Skip to main page content

• HOME
• Current Issue
• Archive
• Alerts
• About ASM
• Contact us
• Tech Support
• Journals.ASM.org

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kasper, L. H. Articles by Brindle, P. K. Search for Related Content PubMed PubMed Citation Articles by Kasper, L. H. Articles by Brindle, P. K.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, February 2006, p. 789-809, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.789-809.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Conditional Knockout Mice Reveal Distinct Functions for the Global Transcriptional Coactivators CBP and p300 in T-Cell Development

Lawryn H. Kasper,¹ Tomofusa Fukuyama,¹ Michelle A. Biesen,¹ Fayçal Boussouar,¹ Caili Tong,³ Antoine de Pauw,² Peter J. Murray,² Jan M. A. van Deursen,³ and Paul K. Brindle^1*

Department of Biochemistry,¹ Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105,² Department of Pediatric and Adolescent Medicine and Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905³

Received 10 July 2005/ Returned for modification 8 August 2005/ Accepted 9 November 2005

Top Abstract Introduction Materials and Methods Results Discussion References

 
The global transcriptional coactivators CREB-binding protein (CBP) and the closely related p300 interact with over 312 proteins, making them among the most heavily connected hubs in the known mammalian protein-protein interactome. It is largely uncertain, however, if these interactions are important in specific cell lineages of adult animals, as homozygous null mutations in either CBP or p300 result in early embryonic lethality in mice. Here we describe a Cre/LoxP conditional p300 null allele (p300^flox) that allows for the temporal and tissue-specific inactivation of p300. We used mice carrying p300^flox and a CBP conditional knockout allele (CBP^flox) in conjunction with an Lck-Cre transgene to delete CBP and p300 starting at the CD4^– CD8^– double-negative thymocyte stage of T-cell development. Loss of either p300 or CBP led to a decrease in CD4⁺ CD8⁺ double-positive thymocytes, but an increase in the percentage of CD8⁺ single-positive thymocytes seen in CBP mutant mice was not observed in p300 mutants. T cells completely lacking both CBP and p300 did not develop normally and were nonexistent or very rare in the periphery, however. T cells lacking CBP or p300 had reduced tumor necrosis factor alpha gene expression in response to phorbol ester and ionophore, while signal-responsive gene expression in CBP- or p300-deficient macrophages was largely intact. Thus, CBP and p300 each supply a surprising degree of redundant coactivation capacity in T cells and macrophages, although each gene has also unique properties in thymocyte development.

Top Abstract Introduction Materials and Methods Results Discussion References

 
CREB-binding protein (CBP) (Crebbp) and p300 (Ep300) are ubiquitously expressed 2,400-residue nuclear phosphoproteins that share 61% overall sequence identity (80 to 90% in evolutionarily conserved domains). Homologs of CBP and p300 are found in Drosophila melanogaster and Caenorhabditis elegans, but there are no other closely related family members in mammals. These two coactivators typically bind to the activation domains of transcription effectors via five unique protein-binding domains (nuclear hormone receptor binding domain, CH1, KIX, CH3, and SID/IBiD) (64, 92). CBP and p300 appear to function redundantly in many instances, but they also have unique properties, particularly in vivo (92). The lack of other closely related family members or conservation of these protein-binding domains in other mammalian proteins implies that CBP and p300 are indispensable.

Following recruitment by transcription factors, juxtaposition of the adaptor, acetyltransferase, and ubiquitin ligase functions of CBP and p300 at the promoter/enhancer is hypothesized to stimulate target gene transcription (92). Histones are believed to be the main acetylation targets of CBP and p300, thereby alleviating repressive chromatin and potentiating transcription, but the ability of CBP and p300 to regulate transcription factor activity by acetylation of specific lysine residues is also thought to be crucial (27, 176, 184). The importance of CBP and p300 for the transcription of endogenous genes, however, has not been widely investigated.

An astonishingly large fraction of the estimated 1,962 (human) transcriptional regulators (134), as well as other proteins, have been shown to interact physically and functionally with CBP and p300 (described interactions now total at least 312) (Fig. 1; more detailed and up to date information is available at http://www.stjude.org/brindle). This number of interactions puts CBP and p300 at the top end of known "connectivity" in the interactome, as high-throughput screens to identify Drosophila, C. elegans, and mammalian interactome networks indicate that only a very small fraction of proteins have as many as 100 to 200 interacting partners (8, 60, 118). It may even be inferred that CBP and p300 interact with the great majority of transcriptional regulators, as most have not been tested. More than half (>190) of the described CBP/p300 interactors are encoded by essential genes in mice (Fig. 1), thus the common assumption that loss of CBP or p300 will have catastrophic effects on specific cell lineages because of broad alterations in gene expression appears reasonable. Also implicit from the high level of connectivity for CBP and p300 is that cells cannot exist in the absence of both coactivators, although it has not been possible to test this rigorously because a conditional knockout allele for p300 has not been available.

View larger version (46K): [in this window] [in a new window]

FIG. 1. The CBP and p300 interactome: 312 viral and mammalian proteins that interact physically or functionally with CBP or p300 in vitro. One hundred ninety-six proteins that are encoded by essential genes in mice (i.e., mutation results in a phenotype) are indicated in boldface type, including 56 genes that are essential for T cells (indicated by an asterisk). The source for phenotype information is Mouse Genome Informatics (http://www.informatics.jax.org/). For more detailed and up to date information on the interactome, see http://www.stjude.org/brindle. References are indicated in parentheses.

It is generally thought that CBP and p300 together are present in limiting amounts in cells, consistent with the view that they are widely involved in transcription (64, 115, 203). Mice that are homozygous for CBP and p300 null alleles, or doubly heterozygous, die during embryogenesis, providing strong evidence for this notion (190, 223). Mice and humans that are haploinsufficient for CBP have developmental defects, also consistent with models that invoke limiting levels of CBP (203). The fact that CBP^–/– and p300^–/– mice survive until about embryonic day 9 (E9), however, shows that many cell types can develop and survive with only CBP or p300.

The roles of CBP and p300 in blood cells are of considerable interest because they are thought to be vital for the function of many hematopoietic transcription factors; at least 65 factors that interact with CBP or p300 are encoded by genes that are essential for T and B cells in mice (Fig. 1). Moreover, chromosomal translocations involving CBP or p300 produce gain-of-function fusion proteins in some types of human leukemia (18) (Fig. 1). Both CBP and p300 are necessary for normal definitive hematopoiesis, including lymphopoiesis, in chimeric mice created with CBP^–/– or p300^–/– embryonic stem cells (164). CBP can also act as a tumor suppressor in hematopoietic cells, including T cells (93), tissue macrophages (histiocytes), and possibly the B-cell lineage (plasmacytomas developed in mice transplanted with CBP heterozygous cells) (109). There is less evidence for p300 acting as a tumor suppressor in hematopoietic cells, although histiocytic sarcoma has been reported in p300^–/– chimeric mice (164). Still, peripheral blood T-cell numbers appear to be mostly unaffected in CBP and p300 heterozygous mice (109), even though CBP and p300 have been implicated by a number of studies as being important for the activity of 56 T-cell-critical transcriptional regulators (Fig. 1). In this regard, conditional knockout of CBP in multiple cell lineages that include thymocytes leads to abnormally high levels of CD8⁺ single-positive (SP) thymocytes (93). In addition, mice that are homozygous for mutations in the CREB- and c-Myb-binding domain (KIX) of p300 have thymic hypoplasia in the context of multilineage hematopoietic defects (95). It is uncertain, however, if CBP and p300 function equivalently in T-cell development. To test the hypothesis that CBP and p300 are each critically limiting in specific cell lineages in vivo, we developed mice with conditional knockout alleles for each gene. We then examined the requirement for CBP and p300 in thymocyte development and their roles in T-cell and macrophage gene expression.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Generation of p300^flox mice. The p300^flox allele was constructed by flanking exon 9 of the mouse Ep300 gene with LoxP sites. DNA for the targeted region was obtained from an E14 Ola mouse embryonic stem (ES) cell genomic DNA phage library. A LoxP site was inserted in the intron 3' of exon 9 using a Tn7 transposon-based system (GPS mutagenesis system, catalog no. 7101; New England Biolabs) with a modified mini-Tn7 vector (pGPS3-PM30-R^1-70-Neo-CAT-TK no. 2; details available upon request) that allowed random insertion of a LoxP site and a selection cassette containing genes for neomycin resistance (Neo), chloramphenicol resistance, and thymidine kinase (TK) flanked by Frt sites (16, 135). A second LoxP site was inserted in the intron 5' of exon 9 using the Tn7 system and another modified mini-Tn7 vector (pGPS3-CAT-R^1-70-LoxP no. 2; details available upon request) (16). In addition, a diphtheria toxin A cassette placed at the 3' end of the targeting construct provided negative selection to reduce the number of nonhomologous targeting events. Mouse ES cells were electroporated with linearized targeting construct and cultured with G418 to positively select for clones that had integrated the targeting construct. Clones were screened by PCR across the 3' end of the targeted region, and positive clones were confirmed by Southern blotting using a StuI digest with a 5' external probe as well as an Asp718/SpeI digest with a 3' external probe to check for homologous targeting. To remove the drug selection cassette, correctly targeted clones were subjected to transient expression of Flp recombinase and treated with 2'-fluoro-2'-deoxy-5-iodouracil-ß-D-arabinofuranoside (FIAU) to enrich for clones that had lost the TK gene (169). Recombination of the Frt sites was confirmed by PCR, and positive clones were checked for loss of the selection cassette by Southern blotting using an XbaI digest and a probe for Neo.

Genotyping of mice. p300 and CBP conditional knockout mice were bred to Lck-Cre transgenic mice (69) or lysM-Cre transgenic mice (32). Recombination of the LoxP sites flanking p300 exon 9 in cells expressing Cre was determined by Southern blotting using an XbaI or EcoRI digest and a cDNA probe to the region encoding amino acids 615 to 681 or by semiquantitative PCR using primers p4 (CTCTACATCCTAAGTGCTAGG), p5 (TGGACTGGTTATCGGTTCACC), and p6 (CAGTAGATGCTAGAGAAAGCC), producing a 540-bp wild-type band, a 720-bp p300 flox band and a 1.1-kb p300^flox band (primer locations shown in Fig. 2). This semiquantitative PCR overestimates the deletion of the p300^flox allele in a systematic manner that was corrected for by using a standard curve of samples of known deletion as determined by quantitative Southern blotting. Generation of CBP conditional knockout mice and PCR genotyping for the deletion of the CBP^flox allele was reported by Kang-Decker et al. (93). Detection of the flox and flox alleles of CBP by Southern blotting was performed using a HindIII digest and a 5' external probe. Thymocyte subpopulations were sorted to check deletion by flow cytometry using anti-CD4 and anti-CD8 antibodies. T cells from the spleen and lymph node were purified to check deletion by positive selection using anti-Thy1.2-conjugated magnetic beads from Miltenyi Biotech.

View larger version (35K): [in this window] [in a new window]

FIG. 2. Generation of the p300 conditional knockout mouse. (a) Gene targeting strategy for the generation of a p300 conditional knockout allele in mice. Exon number and relative position, selection gene cassettes, positions of external and internal Southern blot probes, PCR primer positions, LoxP sites, Frt sites, and restriction sites are indicated. (b) Southern blot using XbaI digest and internal probe showing detection of wild-type, flox, and flox alleles of p300. #1 and #2 are separate p300+/flox; Lck-Cre mice with different deletion efficiencies. (c) Western blot of control and mutant thymocyte nuclear extracts (indicated) using a p300 N-terminal antibody (top panel) and a CBP N-terminal antibody (bottom panel).

Indirect immunofluorescent staining, nuclear extracts, and Western blots. Antibodies against CBP (A-22 and C-20) and p300 (N-15 and C-20) for immunofluorescence and Western blotting were from Santa Cruz. Indirect immunofluorescent detection of CBP and p300 was performed as previously described using single-cell suspensions of thymus and anti-p300 (1:800 dilution, C-20) and anti-CBP (1:800, C-20) antibodies (93). Nuclear extract preparations and Western blots were performed as previously described (95).

Flow cytometry and complete blood count. Antibodies for flow cytometry (fluorescence-activated cell sorting [FACS]) analysis (anti-CD3, anti-CD4, anti-CD8, anti-B220) were purchased from Becton Dickenson. FACS was performed on a FACSCalibur system using CellQuest software. Automated complete blood counts were performed using a Hemavet 3700R.

Estimation of total cell counts. Total counts for thymic subpopulations were determined by multiplying the percentage of cells in a subpopulation as measured by FACS by the total manual viable thymocyte count for that mouse. Cell counts in peripheral blood were estimated from automated complete blood count lymphocyte count per microliter multiplied by the percentages of T cells and B cells in peripheral blood as determined from anti-CD3 versus anti-B220 FACS.

Bone marrow-derived macrophages. Bone marrow-derived macrophages (BMDMs) were obtained by flushing bone cavities and isolating macrophages by differentiation in L-cell-conditioned medium as a source of macrophage colony-stimulating factor as described previously (141).

Activation of splenic T cells and qRT-PCR. Splenic T cells were sorted by FACS and cultured at 2 x 10⁶ cells/ml in Dulbecco's modified Eagle’s medium plus 10% fetal bovine serum with 1 ng/ml phorbol myristate acetate (PMA) and 100 ng/ml ionomycin or dimethyl sulfoxide vehicle for 3 h at 37°C in round-bottom plates. cDNA was generated from 100 ng of total RNA in a 20-µl reaction mixture using Superscript II reverse transcriptase (RT; Invitrogen). Quantitative RT-PCR (qRT-PCR) was performed on an Opticon DNA engine (MJ Research) using 1 µl of cDNA per 25 µl PCR with SYBR green dye. qPCR primers were designed using Primer Express software (Applied Biosystems) and confirmed to yield a single product by melting curve analysis. Samples were normalized to GAPDH mRNA.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Creation of mice with a p300 Cre/LoxP conditional knockout allele. Mouse genomic DNA harboring p300 exons encoding the CREB-binding domain (KIX) was used in the targeting construct. Two LoxP sites were inserted into the introns flanking exon 9, encoding residues 588 to 626 (Fig. 2a); Cre-mediated recombination results in a frameshift mutation if the flanking exons fortuitously splice and a stable mRNA is produced. The equivalent exon is targeted in the CBP^flox allele, so the p300^flox allele is a comparable experimental system (93). Neomycin-resistant ES cell clones were confirmed for correct targeting of the p300 locus by Southern blotting using 5' and 3' probes that were external to the targeting construct (Fig. 2b) (L. H. Kasper, data not shown). The Frt site-flanked drug selection cassette was removed in the ES cells by transient expression of Flp recombinase. Chimeric mice were generated by standard methods, and germ line transmission of the p300^flox allele was achieved. Importantly, p300^flox/flox homozygous mice appeared normal, indicating that the conditional allele is indistinguishable from the wild type in the absence of Cre recombinase. p300^flox recombination in the presence of Cre (yielding p300^flox) was efficient, although it showed considerable variation between mice carrying the Lck-Cre transgene (Fig. 2b). This is likely due to stochastic transgene expression, a relatively common phenomenon in transgenic mice (38).

p300^flox is a null allele. The deletion efficiency in p300^flox/lflox; Lck-Cre mice could be as high as 90 to 95% and was specific for the thymus (L. H. Kasper, data not shown) (69). Mice with high deletion frequencies were deficient for full-length p300 protein as measured by Western blots using thymic nuclear extracts and antibodies specific for the N terminus of p300 (Fig. 2c). CBP protein levels were not measurably affected in the p300 null thymuses (Fig. 2c; 3a), nor were p300 protein levels altered in thymuses deficient for CBP (Fig. 3a). There was no evidence for truncated forms of p300 appearing in p300^flox/lflox; Lck-Cre thymic nuclear extracts as determined by Western blots using an N-terminus-specific antibody following 8% sodium dodecyl sulfate-polyacrylamide gel electrophoresis, although a small amount of material that reacted with a C-terminal p300 antibody ran at the dye front (less than 37 kDa) (P. K. Brindle, data not shown). However, indirect immunofluorescence of thymocytes from p300^flox/flox; Lck-Cre and CBP^flox/flox; Lck-Cre mice using antibodies specific for the C termini of p300 or CBP confirmed that many cells lacked p300 or CBP, respectively (Fig. 3b). Together, these results indicate that p300^flox is a null allele.

View larger version (35K): [in this window] [in a new window]

FIG. 3. Ablation of p300 and CBP protein in mutant thymocytes. (a) Western blot of control and mutant thymocyte whole-cell extracts (indicated) using C-terminal antibodies () to p300 (top panel) and CBP (middle panel) and an antibody against CREB (lower panel). (b) Single-cell suspensions of thymuses from control (p300flox/flox) (upper panels), p300flox/flox; Lck-Cre (middle), and CBPflox/flox; Lck-Cre (lower) mice were stained with 4',6'-diaminido-2-phenylindole (DAPI) to visualize nuclei and antibodies specific for the C termini of p300 or CBP (indicated). Detection was by anti-rabbit immunoglobulin G conjugated with fluorescein isothiocyanate.

Thymic development is abnormal in both CBP^flox/flox; Lck-Cre and p300^flox/flox; Lck-Cre mice. The total number of thymocytes was significantly reduced in both CBP^flox/flox; Lck-Cre mice compared to CBP^flox/flox mice (0.61 x 10⁸ ± 0.17 x 10⁸ [n = 4] versus 2.16 x 10⁸ ± 0.50 x 10⁸ [n = 4]; t test, P = 0.001) and p300^flox/flox; Lck-Cre mice compared to p300^flox/flox mice (1.18 x 10⁸ ± 0.63 x 10⁸ [n = 6] versus 2.22 x 10⁸ ± 0.28 x 10⁸ [n = 6]; t test, P = 0.004). As Lck-Cre mice were found to have thymocyte numbers comparable to those of wild-type mice (T. Fukuyama, data not shown), this deficit is likely caused by inactivation of the floxed alleles.

Quantitation of individual thymocyte subtypes showed that double-negative (DN) cell numbers (the least mature major subtype) were relatively unaffected in both mutants (Fig. 4c and 5c), whereas there was a five- to threefold average decrease in double-positive (DP) cell numbers for CBP (Fig. 4d) (n = 4) and p300 (Fig. 5d) (n = 5) mutant mice, respectively, compared to flox controls (n = 4 and 6, respectively). This apparent conflict with the relative increase in the percentage of DN cells seen by FACS (Fig. 4a and 5a) is explained by the decrease in thymus size for both CBP and p300 mutant mice. Since Lck-Cre transgene expression does not initiate until the DN1 stage (the least mature stage in the thymus), DN cell numbers may be normal (Fig. 4c and 5c) because loss of CBP or p300 has no effect on DN cells or, alternatively, because CBP and p300 protein and mRNA levels are not sufficiently depleted by turnover and dilution until the next stage of development (i.e., DP thymocytes).

View larger version (39K): [in this window] [in a new window]

FIG. 4. CBPflox/flox; Lck-Cre mice have abnormal T-cell subpopulations in the thymus. (a) FACS analysis of thymus, spleen, and peripheral blood from representative control (Lck-Cre, CBPflox/flox) and CBPflox/flox; Lck-Cre mice showing ratios of CD4+ and CD8+ cells. Spleen and peripheral blood were pregated on CD3+ cells. Percentages of cells in relevant quadrants are indicated. (b) Southern blot showing deletion in thymus of CBPflox/flox; Lck-Cre mouse used in panel a. (c to f) Average total counts for the CD4– CD8– DN, CD4+ CD8+ DP, CD4+ SP (CD4 SP), and CD8+ SP (CD8 SP) thymocyte populations in indicated control CBPflox/flox (c to f) (n = 6) and mutant CBPflox/flox; Lck-Cre (c to f) (n = 5) 6-week-old mice (mean ± standard error of the mean).

View larger version (38K): [in this window] [in a new window]

FIG. 5. p300flox/flox; Lck-Cre mice have reduced numbers of the more mature thymocyte subpopulations. (a) FACS analysis of thymus, spleen, and peripheral blood from representative control (Lck-Cre, p300flox/flox) and p300flox/flox; Lck-Cre mice showing ratios of CD4+ and CD8+ cells. Spleen and peripheral blood were pregated on CD3+ cells. Percentages of cells in relevant quadrants are indicated. (b) Southern blot of p300flox/flox; Lck-Cre thymus used in panel a demonstrating efficient deletion. (c to f) Average total counts for the CD4– CD8– DN, CD4+ CD8+ DP, CD4+ SP (CD4 SP), and CD8+ SP (CD8 SP) thymocyte populations in indicated control p300flox/flox (c to f) (n = 4) and mutant p300flox/flox; Lck-Cre (c to f) (n = 4) 6-week-old mice (mean ± standard error of the mean).

SP cell numbers were generally decreased about twofold in the mutants compared to controls (Fig. 4e and f and 5e and f), except that CBP^flox/flox; Lck-Cre mice had normal numbers of CD8⁺ cells (Fig. 4f). This indicates that the 10-fold increase in the percentage of CD8⁺ SP cells in CBP^flox/flox; Lck-Cre thymuses (Fig. 4a) was, in fact, due to a decrease in the absolute number of DP and CD4⁺ SP cells. Given that thymocyte development occurs in a stepwise manner from DN to DP to SP, this would indicate that the "normal" levels of CD8⁺ SP cells in CBP^flox/flox; Lck-Cre mice arise by an altered process, as they are derived from a much smaller pool of DP precursors than in control mice. By contrast, the ratio of CD4⁺ to CD8⁺ SP thymocytes in p300^flox/flox; Lck-Cre mice was normal (Fig. 5a).

We previously showed that CBP^flox/flox; MMTV-Cre mice had an increased percentage of CD8⁺ SP thymocytes, although it was unclear if this defect was autonomous to the thymus because CBP^flox inactivation occurred in multiple tissues (93). Since CBP^flox/flox; Lck-Cre mice also had a marked increase in the percentage of CD8⁺ SP thymocytes compared to Lck-Cre and CBP^flox/flox controls (Fig. 4a), and as the Lck-Cre transgene is expressed exclusively in thymocytes (69), the increase in CD8⁺ SP cells is due to loss of CBP in thymocytes. Together, these results show that CBP and p300 are required for normal thymocyte development, although they have distinct roles in CD8⁺ SP development.

Modest reduction in peripheral T cells in CBP^flox/flox; Lck-Cre mice. Neither CBP^flox/flox; Lck-Cre nor p300^flox/flox; Lck-Cre mice had obviously abnormal proportions of CD4⁺ and CD8⁺ peripheral T cells in the spleen and blood (Fig. 4a; 5a), even when deletion in the thymus was high (80 to 90%) (Fig. 4b; 5b), but there was a modest 2-fold reduction in the number of peripheral blood CD4⁺ (P = 0.028, analysis of variance [ANOVA]) and CD8⁺ (P = 0.020) T cells in CBP^flox/flox; Lck-Cre mice that was not observed in p300^flox/flox; Lck-Cre mice (Fig. 6a). Peripheral blood B-cell numbers were comparable between control and mutant mice, demonstrating the lineage specificity of the mutations (P = 0.58, ANOVA) (Fig. 6b). Comparison of the deletion frequency in thymus and affinity-purified splenic T cells revealed that the fraction of cells harboring the nonrecombined alleles increased in peripheral T cells from p300^flox/flox; Lck-Cre mice (Fig. 7a) and CBP^flox/flox; Lck-Cre mice (Fig. 7b), indicating that late developmental stage or peripheral T cells with p300 or CBP deficiency are at a disadvantage.

View larger version (18K): [in this window] [in a new window]

FIG. 6. Quantitation of peripheral T-cell subpopulations in CBPflox/flox; Lck-Cre and p300flox/flox; Lck-Cre mice. Average numbers of CD4+ and CD8+ T cells (a) and B220+ B cells (b) per microliter of peripheral blood for the indicated genotypes are shown (6- to 9-week-old mice, n = 3 to 9; mean ± standard error of the mean). WT, wild type.

View larger version (22K): [in this window] [in a new window]

FIG. 7. Moderate selection against p300 and CBP null peripheral T cells in p300flox/flox; Lck-Cre and CBPflox/flox; Lck-Cre mice. (a) Representative Southern blot of genomic DNA from thymus and affinity-purified splenic T cells of a p300flox/flox; Lck-Cre mouse indicating relative abundance of the recombined allele. (b) Representative semiquantitative PCR of genomic DNA from thymus and affinity-purified splenic T cells of a CBPflox/flox; Lck-Cre mouse. Splenic T cells were purified by positive selection using Thy1.2+-conjugated magnetic beads.

Loss of p300 in thymocytes does not lead to lymphoma. We previously showed that CBP^flox/flox; MMTV-Cre mice develop T-cell lymphoma with high frequency starting at 3 months of age (93). Since CBP and p300 functions are often interchangeable in vitro, we expected to see T-cell lymphoma develop in p300^flox/flox; MMTV-Cre mice. Surprisingly, a cohort of 40 p300^flox/flox; MMTV-Cre mice did not develop lymphoma out to 104 weeks of age (Fig. 8a). By comparison, a cohort of 37 CBP^flox/flox; MMTV-Cre mice developed T-cell lymphoma with high frequency as early as 16 weeks (Fig. 8a). We observed a comparable incidence and onset of T-cell lymphoma in CBP^flox/flox; Lck-Cre mice (Fig. 8b) (P = 0.03, one-tailed log rank test, n = 25), although over time, the frequency of lymphoma dropped markedly as the mice were backcrossed, indicating that other genetic or environmental factors contribute to tumor development (T. Fukuyama, data not shown). We did not observe lymphoma in p300^flox/flox; Lck-Cre mice out past 1 year of age (Fig. 8c) (n = 21), in agreement with results for the p300^flox/flox; MMTV-Cre mice. The CBP^flox/flox; MMTV-Cre and p300^flox/flox; MMTV-Cre mice were housed in a different facility from the CBP^flox/flox; Lck-Cre and p300^flox/flox; Lck-Cre colonies, suggesting that environmental factors alone cannot account for the differences in tumor phenotype observed. Together, the data support the view that there are intrinsic differences in the tumor suppressor functions of CBP and p300, even though the contributing environmental and genetic factors required for T-cell lymphomagenesis in the absence of CBP are unclear and somewhat variable. In this regard, it has recently been shown that p300 levels can vary in different mouse strains, suggesting that the combined dosage of CBP and p300 protein may also fluctuate and lead to variable phenotypic penetrance (158).

View larger version (15K): [in this window] [in a new window]

FIG. 8. CBP but not p300 deficiency in T cells causes lymphoma with incomplete penetrance. (a to c) Percentage of lymphoma-free surviving CBPflox/flox and p300flox/flox mice with MMTV-Cre (a) or Lck-Cre (b and c). Ages and genotypes of mice are indicated. Mice alive at the end of the study or dying of causes other than lymphoma were censored in the analysis (tick marks). (a) n = 37 to 40, P < 0.0001, one-tailed logrank test; (b) n = 13 to 25, P = 0.03; (c) n = 21 to 24.

CBP and p300 combined dosage is critical for thymocyte development. The ability of T cells to develop and survive with only CBP or p300 raised the possibility that cells lacking both coactivators could be generated. We tested this by creating CBP^flox/flox; p300^flox/flox; Lck-Cre mice ("quad" mutants). Recombination of the CBP^flox allele could be detected in quad mutant thymuses by semiquantitative PCR (Fig. 9b), albeit at a reduced level compared to CBP^flox/flox; Lck-Cre mice. Similar results were obtained for the p300^flox allele (Fig. 9b) (PCR quantitation is fairly linear for CBP^flox but tends to overestimate the relative abundance of the p300^flox allele; M. A. Biesen, data not shown).

View larger version (36K): [in this window] [in a new window]

FIG. 9. CBPflox/flox; p300flox/flox; Lck-Cre mice have abnormal thymocyte subpopulations but essentially normal ratios of peripheral T cells. (a) FACS analysis of thymus, spleen, and peripheral blood from representative control and CBPflox/flox; p300flox/flox; Lck-Cre mice (quad mutant) showing ratios of CD4+ and CD8+ cells. Spleen and peripheral blood were pregated on CD3+ cells. Percentages of cells in relevant quadrants are indicated. (b) Semiquantitative PCR of genomic DNA showing deletion in thymus of CBPflox/flox; p300flox/flox; Lck-Cre mice used in panel a. Quad mutant no. 2 has a higher deletion frequency than no. 1. The p300 PCR tends to overestimate the relative abundance of the p300flox allele.

FACS analysis of quad mutant mice with efficient recombination (50%) of the CBP^flox and p300^flox alleles in the thymus revealed about a 10-fold increase in the percentage of DN thymocytes, with a concomitant decrease in DP cells; mice with a lower deletion frequency (30%) in the thymus had an intermediate immunophenotype (Fig. 9a and b, compare quad mutants 1 and 2). The quad mutant thymuses also lacked the increase in CD8⁺ SP cells that occurred in the CBP^flox/flox; Lck-Cre mice. The proportion of CD4⁺ and CD8⁺ T cells in the spleen and blood of the quad mutants were comparable to Lck-Cre and CBP^flox/flox control mice, however (Fig. 9a).

We did not observe deletion frequencies greater than 50% in quad mutant thymuses, suggesting that thymocytes lacking both CBP and p300 are strongly selected against. We confirmed this by quantitating the number of thymocytes per subpopulation in quad mutants that showed both medium (50%) and low (10 to 30%) deletion frequencies. Total thymocyte counts decreased with increased deletion frequency, and as a result, DN cell numbers were unaffected in both classes of quad mutants compared to control mice (Fig. 10a), but DP cells were reduced about 10-fold in thymuses displaying medium levels of deletion (Fig. 10b). There was a deficiency of SP thymocytes in quad mutants with medium deletion, although the CD8⁺ SP thymocytes were more variably affected (Fig. 10c and d). In further support of these data, genomic DNA isolated from FACS-purified quad mutant thymocyte subtypes showed 30 to 40% deletion of the CBP^flox and p300^flox alleles in DN cells, but there was a steady drop in the frequency of both recombined alleles in DP and SP thymocytes, with an almost complete absence (1% deletion) in peripheral T cells purified from the spleen and lymph nodes (Fig. 11a and b). These results indicate that thymocyte development requires either CBP or p300 and that T cells need CBP or p300 to populate the peripheral lymphoid organs. The numbers of T cells in the spleen and blood of quad mutants were not significantly different from those of control mice, however, indicating that there is compensation by homeostatic proliferation of peripheral T cells that did not recombine the alleles (Fig. 10e and f) (P > 0.05, ANOVA, n = 3 to 9).

View larger version (21K): [in this window] [in a new window]

FIG. 10. Very strong selection against thymocyte subpopulations but not peripheral T cells in CBPflox/flox; p300flox/flox; Lck-Cre mice. Total counts for the CD4– CD8– DN (a), CD4+ CD8+ DP (b), CD4+ SP (CD4 SP) (c), and CD8+ SP (CD8 SP) (d) thymocyte populations of Lck-Cre mice (n = 2), CBPflox/flox; p300flox/flox; Lck-Cre mice (quad mutant) with low deletion (<30%) in whole thymus (n = 3), and CBPflox/flox; p300flox/flox; Lck-Cre mice with medium deletion (30 to 50%, n = 2) in whole thymus (mean ± standard error of the mean). (e) CD3+ T cells per microliter of peripheral blood (mean ± standard error of the mean; n = 4 to 8). Lck-Cre and CBPflox/flox; p300flox/flox (quad) controls are indicated. (f) Ratio of CD3+ to B220+ cells in the spleen as determined by flow cytometry (mean ± standard error of the mean; n = 2 to 3).

View larger version (34K): [in this window] [in a new window]

FIG. 11. Strong selection against thymocyte subpopulations and peripheral T cells lacking both CBP and p300 inCBPflox/flox; p300flox/flox; Lck-Cre mice. Semiquantitative PCR showing deletion of CBPflox (a) and p300flox alleles (b) in FACS-purified CD4– CD8– DN, CD4+ CD8+ DP, CD4+ SP (CD4+ SP), and CD8+ SP (CD8+ SP) thymocyte subpopulations and affinity-purified T cells from spleen and lymph node (LN). T cells from spleen and LN were purified by positive selection using Thy1.2+-conjugated magnetic beads. PCR tends to overestimate the relative abundance of the p300flox allele but is fairly quantitative for CBPflox. Numbers indicate the approximate deletion percentages; p300 values were corrected by comparison to a standard curve of known deletion frequency derived from Southern analysis.

The model that concentrations of CBP and p300 are critically limiting predicts that a modest reduction (50%) in their combined levels will have catastrophic consequences for cells. In contrast, results from this study suggest a model where CBP and p300 are not extremely limiting and that lesser amounts (between 0 and 50%) of the coactivators can still support many critical functions. We compared these models by determining whether one CBP or p300 wild-type allele is sufficient for thymocyte development and for T cells to populate the periphery. Both CBP^+/flox; p300^flox/flox; Lck-Cre and CBP^flox/flox; p300^+/flox; Lck-Cre mice ("triple" mutants) were generated, and semiquantitative PCR analysis of thymic and T-cell genomic DNA was performed. In this instance, we corrected the PCR data by using a standard curve made with samples of known deletion frequency as determined by quantitative Southern blotting. The corrected PCR data demonstrated that triple-mutant cells of both genotypes were selected against in the periphery, although not to the extent seen with the quad mutants (Fig. 12a and b, note that the similarity in deletion frequency for both types of alleles indicates that an individual cell either recombines all the alleles or none; the quad mutant data in Fig. 11 corroborate this). Remarkably, about 20 to 30% deletion was observed for both CBP^flox and p300^flox in peripheral T cells of CBP^+/flox; p300^flox/flox; Lck-Cre mice, suggesting that T cells with one wild-type CBP allele may be able to develop and populate the lymphoid organs to some degree (Fig. 12b). The extent of deletion in peripheral T cells does not depend strongly on the level of deletion in the thymus (compare Fig. 12a and c). All told, these results demonstrate that there is a graded effect of the combined dosage of functional CBP and p300 alleles on T-cell development and their ability to populate the periphery. The inactivation of both CBP alleles (along with one p300 allele) was more detrimental to peripheral T cells than the other triple mutation combination (compare Fig. 12a and c with 12b), which is consistent with our observation that CBP is more important for T cells than p300.

View larger version (20K): [in this window] [in a new window]

FIG. 12. Moderate to strong selection against peripheral T cells lacking three functional alleles of CBP and p300. Percent deletion of CBPflox and p300flox alleles in the thymus and affinity-purified T cells from the spleen and lymph node (LN) of CBPflox/flox; p300+/flox; Lck-Cre (a and c) or CBP+/flox; p300flox/flox; Lck-Cre (b) mice. (c) Deletion frequency in the thymus does not directly impinge on the deletion percentage in the periphery (compare panels b and c). Deletion percentages for CBPflox and p300flox were determined by semiquantitative PCR of genomic DNA corrected for nonlinearity by use of a standard curve made of samples with deletion frequencies determined by quantitative Southern blot.

TCR signal-responsive gene expression is defective in CBP and p300 null splenic T cells. To circumvent inadequate gene deletion in peripheral T cells of CBP^flox/flox; Lck-Cre and p300^flox/flox; Lck-Cre mice, we utilized a reporter transgene, Z/EG that expresses green fluorescent protein (GFP) after Cre-mediated recombination, allowing us to sort for a population of splenic T cells with a high deletion frequency of CBP or p300 (143). We used these cells to elucidate the role of CBP and p300 in gene expression in response to activation of signaling through the T-cell receptor (TCR). We tested two genes, interleukin-2 (IL-2) and tumor necrosis factor alpha (TNF-), whose expression in response to TCR signaling is critical for T-cell function and has been reported to involve p300 and CBP (47, 228). IL-2 mRNA expression was reduced less than twofold in CBP^flox/flox; Lck-Cre cells and was unaffected in p300^flox/flox; Lck-Cre splenic T cells in response to treatment with PMA and calcium ionophore. The decrease in IL-2 may be due to the increased fraction of CD8⁺ T cells relative to CD4⁺ cells in the spleen (Fig. 4a), as not all CD8⁺-T-cell subtypes express IL-2 efficiently (212). TNF- mRNA expression, however, was decreased more than twofold in p300^flox/flox; Lck-Cre and more than fourfold in CBP^flox/flox; Lck-Cre in activated splenic T cells (Fig. 13a and b). This deficit in TNF- expression is in agreement with a previous report by Falvo et al. demonstrating that CBP null heterozygous T cells are defective in TNF- expression in response to TCR activation with anti-CD3 and suggests that p300 is also important (47).

View larger version (16K): [in this window] [in a new window]

FIG. 13. Examination of endogenous TCR-signaling-responsive gene expression in splenic T cells lacking p300 or CBP. (a and b) Splenocytes from mice bearing Lck-Cre and Z/EG reporter transgenes were sorted for GFP-expressing control (Lck-Cre; Z/EG), p300 null (p300flox/flox; Lck-Cre; Z/EG), or CBP null (p300flox/flox; Lck-Cre; Z/EG) splenic T cells. Cells were treated ex vivo with 1 ng/ml PMA and 200 ng/ml calcium ionophore (Iono) for 3 h, and qRT-PCR was performed to determine mRNA expression of IL-2 (a) and TNF- (b). Expression was normalized to GAPDH expression, and treated control cells were arbitrarily set to 100 in each experiment. Graphs represent the average results from two independent experiments using cells from two different mice of each genotype (n = 2).

Gene expression in CBP and p300 null macrophages. We used bone marrow-derived macrophages to further investigate the effects of CBP and p300 deficiency on endogenous signal-responsive gene expression. We chose several cytokine- and Toll-like receptor (TLR)-responsive target genes where either CBP or p300 has been previously implicated as playing a key role in expression or a presumed role based on chromatin immunoprecipitation assays. TNF-, arginase (Arg1), inducible nitric oxide synthase (iNOS), and interferon regulatory factor 1 (IRF-1), are regulated by gene-specific combinations of the CBP/p300-interacting transcription factors ATF-2, c-Jun, SP1, Ets, Egr-1, NF-B, AP-1, STAT1, PU.1, STAT6, and C/EBPß (Fig. 1) (9, 117, 152). CBP^flox/flox; lysMcre mice that express Cre in macrophages yielded cells with an 80 to 90% reduction in CBP protein when measured by Western blotting of nuclear extracts (Fig. 14a) (32). Northern blot analysis revealed that TNF- mRNA was robustly induced in response to lipopolysaccharide (LPS) stimulation in CBP^flox/flox; lysMcre macrophages, although not quite as well as in control CBP^flox/flox cells (Fig. 14b) (rRNA served as a loading control). Arginase (Arg1) induction in response to the cytokine IL-4 was measured by Western blotting and was comparable between CBP^flox/flox; lysMcre and CBP^flox/flox macrophages (Fig. 14c) (the nonspecific band serves as a loading control).

View larger version (68K): [in this window] [in a new window]

FIG. 14. Examination of endogenous gene expression in BMDMs deficient for either CBP or p300. (a) lysMcre-mediated loss of CBP in BMDMs (left panel). Nuclear extracts from BMDMs cultured ex vivo from CBPflox/flox or two different CBPflox/flox; lysMcre mice showed CBP deficiency as measured by immunoblotting with CBP-specific antisera. p300 levels were unaffected. (Right panel) p300 deletion in BMDMs was confirmed by semiquantitative PCR of genomic DNA. (b) Normal CBP levels are not required for the TLR4-mediated induction of TNF- expression. Northern blot analysis of TNF- mRNA induction in response to stimulation through the TLR4 pathway. BMDMs were plated at 2 x 106 cells per well and stimulated with Escherichia coli LPS at 100 ng/ml for the times indicated. RNA was isolated and probed with a TNF- cDNA probe. Ethidium bromide-stained rRNA is the loading control (bottom panels). (c) CBP is not required for the IL-4-mediated induction of arginase 1 (Arg1) expression. BMDMs were stimulated with IL-4 (10 ng/ml) or left unstimulated (–) for the times shown, and lysates were analyzed for Arg1 expression by immunoblotting. The nonspecific band serves as a loading control (asterisk). (d) Normal p300 levels are not required for the TLR4-mediated induction of TNF- expression. Total RNA was isolated and analyzed as shown in panel b. (e) Normal p300 levels are not required for the IL-4-mediated induction of Arg1 expression. BMDMs were plated and stimulated with IL-4 as shown in panel c. (f) Normal p300 levels are not required for the IFN--mediated induction of IRF-1 expression but may be required for the normal kinetics of iNOS production. BMDMs were stimulated with LPS and IFN- to induce the expression of IRF-1 and iNOS, and lysates were analyzed by immunoblotting. The nonspecific band serves as a loading control (asterisk). Note that although IRF-1 levels are normal in p300flox/flox; lysMcre BMDMs compared to control cells, the induction of iNOS expression is slightly delayed at the 6-h time point but eventually reaches robust levels.

We next examined gene expression in macrophages deficient for p300. Recombination of the p300^flox allele in p300^flox/flox; lysMcre macrophages was confirmed by semiquantitative PCR of genomic DNA (Fig. 14a). TNF- mRNA was induced comparably by LPS in p300^flox/flox and p300^flox/flox; lysMcre macrophages (Fig. 14d, rRNA loading control in bottom panel). Arg1 induction after IL-4 stimulation was also comparable between p300^flox/flox and p300^flox/flox; lysMcre macrophages (Fig. 14e), although treatment with both gamma interferon (IFN-) and LPS revealed a modest deficit in the kinetics of iNOS expression but not IRF-1 (Fig. 14f, nonspecific band acts as a loading control). IRF-1 and iNOS expression in response to the same stimuli in CBP^flox/flox; lysMcre macrophages was in the normal range (P. J. Murray, data not shown). Together, these results indicate that CBP or p300 individually is not highly limiting for TNF- and Arg1 expression in macrophages in response to LPS and IL-4. Interestingly, iNOS, but not IRF-1, induction in response to IFN- plus LPS appears to be partially sensitive to p300 deficiency, consistent with a proposed model that CBP and p300 are limiting for iNOS transcription (117). Induction of high-level iNOS expression requires IRF-1 and NF-B activity, so it appears that p300 levels are important for this process but expression levels can be compensated for by CBP or other factors. We did not observe a noticeable defect in TNF- induction in macrophages even though both CBP and p300 null T cells showed a clear deficit (Fig. 13b) and B cells deficient for p300 or CBP showed a 30 to 60% decrease in TNF- expression in response to B-cell receptor signaling (P. K. Brindle, submitted for publication). This may reflect different transcriptional regulator usage in the three cell types. It is worth noting that the macrophages tested here had less than 100% inactivation of CBP^flox or p300^flox, so it is possible that contributions to gene expression by CBP or p300 were underestimated in this analysis.

Top Abstract Introduction Materials and Methods Results Discussion References

 
Inactivation of either CBP or p300 starting at the DN stage of thymocyte development reduced, but did not completely block, the ability of T cells to populate the periphery; whereas, inactivation of all four CBP and p300 alleles had strong negative effects on T-cell development in the thymus. In addition, the aberrant increase in the percentage of CD8⁺ SP thymocytes seen in CBP^flox/flox; Lck-Cre mice was not observed in p300^flox/flox; Lck-Cre animals, indicating that CBP and p300 have nonredundant roles in T-cell development. Although the absolute levels of CBP and p300 protein are unknown, thymocytes express both proteins, which implies that large differences in expression do not account for the phenotypes. A provocative possibility is that differences in the biochemical properties of CBP and p300 are fundamental to the production of normal T cells and may also explain why loss of CBP, but not p300, in T cells can result in lymphoma.

Homeostatic proliferative mechanisms largely compensated for any reduction in the number of naive peripheral T cells caused by the mutations by allowing cells that did not recombine the conditional alleles (likely due to stochastic expression of the Lck-Cre transgene) to expand and fill the niche (84). It is somewhat counterintuitive that loss of both CBP and p300 did not cause a significant decrease in peripheral T cells, even though loss of CBP alone caused a modest 2-fold deficit. There are several possible explanations for this observation. First, T cells lacking CBP alone may function in a non-cell-autonomous manner to suppress homeostatic proliferation of peripheral T cells. For example, it is possible that less IL-7, an essential cytokine for homeostatic proliferation, is available in CBP^flox/flox; Lck-Cre mice (84). Since T cells lacking both CBP and p300 are very rare or nonexistent outside the thymus, homeostatic proliferation would function normally in CBP^flox/flox; p300^flox/flox; Lck-Cre mice in this scenario. Second, homeostatic "cell counting" or "empty space detection" mechanisms may respond more efficiently to a strong deficit in early thymocyte development (as seen in CBP^flox/flox; p300^flox/flox; Lck-Cre mice) than if cells are less severely affected in the thymus, as with CBP^flox/flox; Lck-Cre mice. Third, recombination of the floxed alleles may be more efficient in CBP^flox/flox; Lck-Cre mice than in CBP^flox/flox; p300^flox/flox; Lck-Cre mice, thus homeostatic proliferation may be unable to completely fill the larger empty niche in the former.

It was surprising that loss of either CBP or p300 alone did not result in a more drastic T-cell phenotype given that the two coactivators have been shown to interact in vitro with over 190 proteins encoded by essential genes in mice, of which at least 56 are crucial for T cells (Mouse Genome Informatics) (Fig. 1). It is possible that these two coactivators are not generally limiting in cells to the extent previously believed (64, 115, 203). Indeed, CBP^–/– and p300^–/– mice are viable through the first half of development (dying at E9 to E11.5), suggestive of three possibilities with regard to the in vivo roles of CBP and p300. (i) In vitro interactions with CBP and p300 may not be biologically relevant. Our findings, however, argue that CBP and p300 interactions based upon in vitro evidence cannot be dismissed out of hand. Although HDM2 appears to aggregate nonspecifically with the unfolded TAZ1 domain of p300 in the presence of EDTA (131), we have found that three essential transcription factors (CREB, c-Myb, and HIF-1) with well-characterized in vitro interactions with CBP and p300 show partial loss of activity when CBP and p300 functionality is attenuated by mutation in primary cells or mice (95; Kasper et al., in press). (ii) CBP and p300 may function redundantly in most instances and be generally nonlimiting in many cell types. Support for the second point is self-evident, since many T cells can develop and survive and mice can go through a substantial portion of development with either CBP or p300 alone. In addition, we have not observed increased expression of remaining wild-type alleles as a possible compensatory mechanism in mutant cells, so it appears that CBP and p300 levels are not highly limiting for some of their functions. Nevertheless, there are differences in the phenotypes of the various CBP and p300 mutant mice created to date, making it clear that there are either unique biochemical properties for each coactivator or that some cell types have a skewed ratio of CBP to p300 that makes one of them limiting upon mutation. (iii) Other transcriptional cofactors that are not highly related to CBP and p300 may supply redundant functions (e.g., other proteins that have histone acetyltransferase activity and bromodomains such as Gcn5, P/CAF, and TAF1). This point raises the prospect that coactivator networks are more broadly interconnected and robust than typically understood. But there are obviously limits to this proposition, as our studies show that either CBP or p300 is absolutely essential because T cells lacking both are not viable. So other cofactors may only be able to compensate under a limited number of situations. The identities of such factors are unknown, although recent genetic studies demonstrate that the combined dosage of various histone acetyltransferase proteins harboring bromodomains (p300 and Gcn5, and p300 and P/CAF) are not generally limiting for mouse development (158).

The creation of CBP^flox and p300^flox mice will now permit researchers to rigorously test whether either member of this small coactivator family is critical in specific cell lineages in vivo and to test their roles in endogenous gene expression ex vivo. Such analyses would be facilitated by the use of a Cre recombination-dependent GFP indicator allele to enable the FACS purification of cells with high frequencies (>90%) of floxed gene inactivation for functional and transcriptional studies ex vivo (143).

 
We thank S. Lerach and C. Barlow for excellent technical assistance; the Transgenic core; R. Cross, J. Gatewood, J. Smith, and the Mouse Immunophenotyping core; R. Ashmun and the Flow Cytometry and Cell Sorting Shared Resource; the Animal Resource Center facilities at SJCRH; M. Biery, N. Craig, G. Martin, and S. Fiering for plasmids; and J. Opferman for helpful comments. The Hartwell Center at SJCRH provided oligonucleotides and DNA sequencing.

This work was supported by NCI grant RO1 CA076385 (to P.K.B.), the Cancer Center (CORE) support grant P30 CA021765, and by the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital.

 
* Corresponding author. Mailing address: Department of Biochemistry, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-2522. Fax: (901) 525-8025. E-mail: paul.brindle{at}stjude.org.

Top Abstract Introduction Materials and Methods Results Discussion References

 

1
1. Asahara, H., S. Tartare-Deckert, T. Nakagawa, T. Ikehara, F. Hirose, T. Hunter, T. Ito, and M. Montminy. 2002. Dual roles of p300 in chromatin assembly and transcriptional activation in cooperation with nucleosome assembly protein 1 in vitro. Mol. Cell. Biol. 22:2974-2983.[Abstract/Free Full Text]
2
2. Bachurski, C. J., G. H. Yang, T. A. Currier, R. M. Gronostajski, and D. Hong. 2003. Nuclear factor I/thyroid transcription factor 1 interactions modulate surfactant protein C transcription. Mol. Cell. Biol. 23:9014-9024.[Abstract/Free Full Text]
3
3. Bai, L., and J. L. Merchant. 2000. Transcription factor ZBP-89 cooperates with histone acetyltransferase p300 during butyrate activation of p21waf1 transcription in human cells. J. Biol. Chem. 275:30725-30733.[Abstract/Free Full Text]
4
4. Bai, R. Y., C. Koester, T. Ouyang, S. A. Hahn, M. Hammerschmidt, C. Peschel, and J. Duyster. 2002. SMIF, a Smad4-interacting protein that functions as a co-activator in TGFbeta signalling. Nat. Cell Biol. 4:181-190.[CrossRef][Medline]
5
5. Bailey, P., V. Sartorelli, Y. Hamamori, and G. E. Muscat. 1998. The orphan nuclear receptor, COUP-TF II, inhibits myogenesis by post-transcriptional regulation of MyoD function: COUP-TF II directly interacts with p300 and myoD. Nucleic Acids Res. 26:5501-5510.[Abstract/Free Full Text]
6
6. Bannert, N., A. Avots, M. Baier, E. Serfling, and R. Kurth. 1999. GA-binding protein factors, in concert with the coactivator CREB binding protein/p300, control the induction of the interleukin 16 promoter in T lymphocytes. Proc. Natl. Acad. Sci. USA 96:1541-1546.[Abstract/Free Full Text]
7
7. Barbacci, E., A. Chalkiadaki, C. Masdeu, C. Haumaitre, L. Lokmane, C. Loirat, S. Cloarec, I. Talianidis, C. Bellanne-Chantelot, and S. Cereghini. 2004. HNF1ß/TCF2 mutations impair transactivation potential through altered co-regulator recruitment. Hum. Mol. Genet. 13:3139-3149.[Abstract/Free Full Text]
8
8. Barrios-Rodiles, M., K. R. Brown, B. Ozdamar, R. Bose, Z. Liu, R. S. Donovan, F. Shinjo, Y. Liu, J. Dembowy, I. W. Taylor, V. Luga, N. Przulj, M. Robinson, H. Suzuki, Y. Hayashizaki, I. Jurisica, and J. L. Wrana. 2005. High-throughput mapping of a dynamic signaling network in mammalian cells. Science 307:1621-1625.[Abstract/Free Full Text]
9
9. Barthel, R., A. V. Tsytsykova, A. K. Barczak, E. Y. Tsai, C. C. Dascher, M. B. Brenner, and A. E. Goldfeld. 2003. Regulation of tumor necrosis factor alpha gene expression by mycobacteria involves the assembly of a unique enhanceosome dependent on the coactivator proteins CBP/p300. Mol. Cell. Biol. 23:526-533.[Abstract/Free Full Text]
10
10. Bavner, A., J. Matthews, S. Sanyal, J. A. Gustafsson, and E. Treuter. 2005. EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation. Nucleic Acids Res. 33:3561-3569.[Abstract/Free Full Text]
11
11. Bereshchenko, O. R., W. Gu, and R. Dalla-Favera. 2002. Acetylation inactivates the transcriptional repressor BCL6. Nat. Genet. 32:606-613.[CrossRef][Medline]
12
12. Bernat, A., N. Avvakumov, J. S. Mymryk, and L. Banks. 2003. Interaction between the HPV E7 oncoprotein and the transcriptional coactivator p300. Oncogene 22:7871-7881.[CrossRef][Medline]
13
13. Bessa, M., M. K. Saville, and R. J. Watson. 2001. Inhibition of cyclin A/Cdk2 phosphorylation impairs B-Myb transactivation function without affecting interactions with DNA or the CBP coactivator. Oncogene 20:3376-3386.[CrossRef][Medline]
14
14. Bhakat, K. K., T. Izumi, S. H. Yang, T. K. Hazra, and S. Mitra. 2003. Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene. EMBO J. 22:6299-6309.[CrossRef][Medline]
15
15. Bhattacharya, S., C. L. Michels, M. K. Leung, Z. P. Arany, A. L. Kung, and D. M. Livingston. 1999. Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev. 13:64-75.[Abstract/Free Full Text]
16
16. Biery, M. C., F. J. Stewart, A. E. Stellwagen, E. A. Raleigh, and N. L. Craig. 2000. A simple in vitro Tn7-based transposition system with low target site selectivity for genome and gene analysis. Nucleic Acids Res. 28:1067-1077.[Abstract/Free Full Text]
17
17. Billon, N., D. Carlisi, M. B. Datto, L. A. van Grunsven, A. Watt, X. F. Wang, and B. B. Rudkin. 1999. Cooperation of Sp1 and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation. Oncogene 18:2872-2882.[CrossRef][Medline]
18
18. Blobel, G. A. 2002. CBP and p300: versatile coregulators with important roles in hematopoietic gene expression. J. Leukoc. Biol. 71:545-556.[Free Full Text]
19
19. Bouras, T., M. Fu, A. A. Sauve, F. Wang, A. A. Quong, N. D. Perkins, R. T. Hay, W. Gu, and R. G. Pestell. 2005. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J. Biol. Chem. 280:10264-10276.[Abstract/Free Full Text]
20
20. Bowen, H., A. Lapham, E. Phillips, I. Yeung, M. Alter-Koltunoff, B. Z. Levi, V. H. Perry, D. A. Mann, and C. H. Barton. 2003. Characterization of the murine Nramp1 promoter: requirements for transactivation by Miz-1. J. Biol. Chem. 278:36017-36026.[Abstract/Free Full Text]
21
21. Braganca, J., J. J. Eloranta, S. D. Bamforth, J. C. Ibbitt, H. C. Hurst, and S. Bhattacharya. 2003. Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2. J. Biol. Chem. 278:16021-16029.[Abstract/Free Full Text]
22
22. Braganca, J., T. Swingler, F. I. Marques, T. Jones, J. J. Eloranta, H. C. Hurst, T. Shioda, and S. Bhattacharya. 2002. Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2. J. Biol. Chem. 277:8559-8565.[Abstract/Free Full Text]
23
23. Burysek, L., W. S. Yeow, B. Lubyova, M. Kellum, S. L. Schafer, Y. Q. Huang, and P. M. Pitha. 1999. Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J. Virol. 73:7334-7342.[Abstract/Free Full Text]
24
24. Castillo, A. I., A. M. Jimenez-Lara, R. M. Tolon, and A. Aranda. 1999. Synergistic activation of the prolactin promoter by vitamin D receptor and GHF-1: role of the coactivators, CREB-binding protein and steroid hormone receptor coactivator-1 (SRC-1). Mol. Endocrinol. 13:1141-1154.[Abstract/Free Full Text]
25
25. Chakraborty, S., V. Senyuk, S. Sitailo, Y. Chi, and G. Nucifora. 2001. Interaction of EVI1 with cAMP-responsive element-binding protein-binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles. J. Biol. Chem. 276:44936-44943.[Abstract/Free Full Text]
26
26. Chan, H. M., M. Krstic-Demonacos, L. Smith, C. Demonacos, and N. B. La Thangue. 2001. Acetylation control of the retinoblastoma tumour-suppressor protein. Nat. Cell Biol. 3:667-674.[CrossRef][Medline]
27
27. Chan, H. M., and N. B. La Thangue. 2001. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J. Cell Sci. 114:2363-2373.[Abstract/Free Full Text]
28
28. Chang, C. W., H. C. Chuang, C. Yu, T. P. Yao, and H. Chen. 2005. Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol. Cell. Biol. 25:8401-8414.[Abstract/Free Full Text]
29
29. Chen, J., S. S. Halappanavar, J. R. St-Germain, B. K. Tsang, and Q. Li. 2004. Role of Akt/protein kinase B in the activity of transcriptional coactivator p300. Cell. Mol. Life Sci. 61:1675-1683.[Medline]
30
30. Chen, J., J. R. St-Germain, and Q. Li. 2005. B56 Regulatory subunit of protein phosphatase 2A mediates valproic acid-induced p300 degradation. Mol. Cell. Biol. 25:525-532.[Abstract/Free Full Text]
31
31. Chen, Q., D. H. Dowhan, D. Liang, D. D. Moore, and P. A. Overbeek. 2002. CREB-binding protein/p300 co-activation of crystallin gene expression. J. Biol. Chem. 277:24081-24089.[Abstract/Free Full Text]
32
32. Clausen, B. E., C. Burkhardt, W. Reith, R. Renkawitz, and I. Forster. 1999. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 8:265-277.[CrossRef][Medline]
33
33. Cotter, M. A., II, and E. S. Robertson. 2000. Modulation of histone acetyltransferase activity through interaction of Epstein-Barr nuclear antigen 3C with prothymosin alpha. Mol. Cell. Biol 20:5722-5735.[Abstract/Free Full Text]
34
34. Dai, P., H. Akimaru, Y. Tanaka, T. Maekawa, M. Nakafuku, and S. Ishii. 1999. Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by GLI3. J. Biol. Chem. 274:8143-8152.[Abstract/Free Full Text]
35
35. Dai, Y. S., P. Cserjesi, B. E. Markham, and J. D. Molkentin. 2002. The transcription factors GATA4 and dHAND physically interact to synergistically activate cardiac gene expression through a p300-dependent mechanism. J. Biol. Chem. 277:24390-24398.[Abstract/Free Full Text]
36
36. Dai, Y. S., and B. E. Markham. 2001. p300 Functions as a coactivator of transcription factor GATA-4. J. Biol. Chem. 276:37178-37185.[Abstract/Free Full Text]
37
37. De Leo, R., S. Miccadei, E. Zammarchi, and D. Civitareale. 2000. Role for p300 in Pax 8 induction of thyroperoxidase gene expression. J. Biol. Chem. 275:34100-34105.[Abstract/Free Full Text]
38
38. Dietrich, P., I. Dragatsis, S. Xuan, S. Zeitlin, and A. Efstratiadis. 2000. Conditional mutagenesis in mice with heat shock promoter-driven cre transgenes. Mamm. Genome 11:196-205.[CrossRef][Medline]
39
39. Doucas, V., M. Tini, D. A. Egan, and R. M. Evans. 1999. Modulation of CREB binding protein function by the promyelocytic (PML) oncoprotein suggests a role for nuclear bodies in hormone signaling. Proc. Natl. Acad. Sci. USA 96:2627-2632.[Abstract/Free Full Text]
40
40. Dowell, P., J. E. Ishmael, D. Avram, V. J. Peterson, D. J. Nevrivy, and M. Leid. 1997. p300 functions as a coactivator for the peroxisome proliferator-activated receptor alpha. J. Biol. Chem. 272:33435-33443.[Abstract/Free Full Text]
41
41. Eckner, R., T. P. Yao, E. Oldread, and D. M. Livingston. 1996. Interaction and functional collaboration of p300/CBP and bHLH proteins in muscle and B-cell differentiation. Genes Dev. 10:2478-2490.[Abstract/Free Full Text]
42
42. Ema, M., K. Hirota, J. Mimura, H. Abe, J. Yodoi, K. Sogawa, L. Poellinger, and Y. Fujii-Kuriyama. 1999. Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J. 18:1905-1914.[CrossRef][Medline]
43
43. Emelyanov, A. V., C. R. Kovac, M. A. Sepulveda, and B. K. Birshtein. 2002. The interaction of Pax5 (BSAP) with Daxx can result in transcriptional activation in B cells. J. Biol. Chem. 277:11156-11164.[Abstract/Free Full Text]
44
44. Erickson, R. L., N. Hemati, S. E. Ross, and O. A. MacDougald. 2001. p300 coactivates the adipogenic transcription factor CCAAT/enhancer-binding protein alpha. J. Biol. Chem. 276:16348-16355.[Abstract/Free Full Text]
45
45. Ernst, P., J. Wang, M. Huang, R. H. Goodman, and S. J. Korsmeyer. 2001. MLL and CREB bind cooperatively to the nuclear coactivator CREB-binding protein. Mol. Cell. Biol. 21:2249-2258.[Abstract/Free Full Text]
46
46. Facchinetti, V., L. Loffarelli, S. Schreek, M. Oelgeschlager, B. Luscher, M. Introna, and J. Golay. 1997. Regulatory domains of the A-Myb transcription factor and its interaction with the CBP/p300 adaptor molecules. Biochem. J. 324:729-736.[Medline]
47
47. Falvo, J. V., B. M. Brinkman, A. V. Tsytsykova, E. Y. Tsai, T. P. Yao, A. L. Kung, and A. E. Goldfeld. 2000. A stimulus-specific role for CREB-binding protein (CBP) in T cell receptor-activated tumor necrosis factor alpha gene expression. Proc. Natl. Acad. Sci. USA 97:3925-3929.[Abstract/Free Full Text]
48
48. Fang, X., E. K. Stachowiak, S. M. Dunham-Ems, I. Klejbor, and M. K. Stachowiak. 2005. Control of CREB-binding protein signaling by nuclear fibroblast growth factor receptor-1: a novel mechanism of gene regulation. J. Biol. Chem. 280:28451-28462.[Abstract/Free Full Text]
49
49. Faniello, M. C., M. A. Bevilacqua, G. Condorelli, B. de Crombrugghe, S. N. Maity, V. E. Avvedimento, F. Cimino, and F. Costanzo. 1999. The B subunit of the CAAT-binding factor NFY binds the central segment of the Co-activator p300. J. Biol. Chem. 274:7623-7626.[Abstract/Free Full Text]
50
50. Felzien, L. K., C. Woffendin, M. O. Hottiger, R. A. Subbramanian, E. A. Cohen, and G. J. Nabel. 1998. HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator. Proc. Natl. Acad. Sci. USA 95:5281-5286.[Abstract/Free Full Text]
51
51. Fryer, C. J., E. Lamar, I. Turbachova, C. Kintner, and K. A. Jones. 2002. Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex. Genes Dev. 16:1397-1411.[Abstract/Free Full Text]
52
52. Fu, M., C. Wang, M. Rao, X. Wu, T. Bouras, X. Zhang, Z. Li, X. Jiao, J. Yang, A. Li, N. D. Perkins, B. Thimmapaya, A. L. Kung, A. Munoz, A. Giordano, M. P. Lisanti, and R. G. Pestell. 2005. Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism. J. Biol. Chem. 280:29728-29742.[Abstract/Free Full Text]
53
53. Fujii, Y., A. Kumatori, and M. Nakamura. 2003. SATB1 makes a complex with p300 and represses gp91(phox) promoter activity. Microbiol. Immunol. 47:803-811.[Medline]
54
54. Fukuda, S., T. Kondo, H. Takebayashi, and T. Taga. 2004. Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway. Cell Death Differ. 11:196-202.[CrossRef][Medline]
55
55. Furia, B., L. Deng, K. Wu, S. Baylor, K. Kehn, H. Li, R. Donnelly, T. Coleman, and F. Kashanchi. 2002. Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins. J. Biol. Chem. 277:4973-4980.[Abstract/Free Full Text]
56
56. Fuse, H., H. Kitagawa, and S. Kato. 2000. Characterization of transactivational property and coactivator mediation of rat mineralocorticoid receptor activation function-1 (AF-1). Mol. Endocrinol. 14:889-899.[Abstract/Free Full Text]
57
57. Garcia-Rodriguez, C., and A. Rao. 1998. Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP). J. Exp. Med. 187:2031-2036.[Abstract/Free Full Text]
58
58. Gingras, S., J. Simard, B. Groner, and E. Pfitzner. 1999. p300/CBP is required for transcriptional induction by interleukin-4 and interacts with Stat6. Nucleic Acids Res. 27:2722-2729.[Abstract/Free Full Text]
59
59. Giordano, A., and M. L. Avantaggiati. 1999. p300 and CBP: partners for life and death. J. Cell. Physiol. 181:218-230.[CrossRef][Medline]
60
60. Giot, L., J. S. Bader, C. Brouwer, A. Chaudhuri, B. Kuang, Y. Li, Y. L. Hao, C. E. Ooi, B. Godwin, E. Vitols, G. Vijayadamodar, P. Pochart, H. Machineni, M. Welsh, Y. Kong, B. Zerhusen, R. Malcolm, Z. Varrone, A. Collis, M. Minto, S. Burgess, L. McDaniel, E. Stimpson, F. Spriggs, J. Williams, K. Neurath, N. Ioime, M. Agee, E. Voss, K. Furtak, R. Renzulli, N. Aanensen, S. Carrolla, E. Bickelhaupt, Y. Lazovatsky, A. DaSilva, J. Zhong, C. A. Stanyon, R. L. Finley, Jr., K. P. White, M. Braverman, T. Jarvie, S. Gold, M. Leach, J. Knight, R. A. Shimkets, M. P. McKenna, J. Chant, and J. M. Rothberg. 2003. A protein interaction map of Drosophila melanogaster. Science 302:1727-1736.[Abstract/Free Full Text]
61
61. Girdwood, D., D. Bumpass, O. A. Vaughan, A. Thain, L. A. Anderson, A. W. Snowden, E. Garcia-Wilson, N. D. Perkins, and R. T. Hay. 2003. P300 transcriptional repression is mediated by SUMO modification. Mol. Cell 11:1043-1054.[CrossRef][Medline]
62
62. Gizard, F., B. Lavallee, F. DeWitte, and D. W. Hum. 2001. A novel zinc finger protein TReP-132 interacts with CBP/p300 to regulate human CYP11A1 gene expression. J. Biol. Chem. 276:33881-33892.[Abstract/Free Full Text]
63
63. Gomez-Gonzalo, M., I. Benedicto, M. Carretero, E. Lara-Pezzi, A. Maldonado-Rodriguez, R. Moreno-Otero, M. M. Lai, and M. Lopez-Cabrera. 2004. Hepatitis C virus core protein regulates p300/CBP co-activation function. Possible role in the regulation of NF-AT1 transcriptional activity. Virology 328:120-130.[CrossRef][Medline]
64
64. Goodman, R. H., and S. Smolik. 2000. CBP/p300 in cell growth, transformation, and development. Genes Dev. 14:1553-1577.[Free Full Text]
65
65. Gronroos, E., U. Hellman, C. H. Heldin, and J. Ericsson. 2002. Control of Smad7 stability by competition between acetylation and ubiquitination. Mol. Cell 10:483-493.[CrossRef][Medline]
66
66. Guidez, F., L. Howell, M. Isalan, M. Cebrat, R. M. Alani, S. Ivins, I. Hormaeche, M. J. McConnell, S. Pierce, P. A. Cole, J. Licht, and A. Zelent. 2005. Histone acetyltransferase activity of p300 is required for transcriptional repression by the promyelocytic leukemia zinc finger protein. Mol. Cell. Biol. 25:5552-5566.[Abstract/Free Full Text]
67
67. Hasan, S., P. O. Hassa, R. Imhof, and M. O. Hottiger. 2001. Transcription coactivator p300 binds PCNA and may have a role in DNA repair synthesis. Nature 410:387-391.[CrossRef][Medline]
68
68. Hashimoto, K., K. Zanger, A. N. Hollenberg, L. E. Cohen, S. Radovick, and F. E. Wondisford. 2000. cAMP response element-binding protein-binding protein mediates thyrotropin-releasing hormone signaling on thyrotropin subunit genes. J. Biol. Chem. 275:33365-33372.[Abstract/Free Full Text]
69
69. Hennet, T., F. K. Hagen, L. A. Tabak, and J. D. Marth. 1995. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc. Natl. Acad. Sci. USA 92:12070-12074.[Abstract/Free Full Text]
70
70. Hirai, M., K. Ono, T. Morimoto, T. Kawamura, H. Wada, T. Kita, and K. Hasegawa. 2004. FOG-2 competes with GATA-4 for a transcriptional coactivator p300 and represses hypertrophic responses in cardiac myocytes. J. Biol. Chem. 279:37640-37650.[Abstract/Free Full Text]
71
71. Hirose, T., R. Fujii, H. Nakamura, S. Aratani, H. Fujita, M. Nakazawa, K. Nakamura, K. Nishioka, and T. Nakajima. 2003. Regulation of CREB-mediated transcription by association of CDK4 binding protein p34SEI-1 with CBP. Int. J. Mol. Med. 11:705-712.[Medline]
72
72. Hoffmeister, A., A. Ropolo, S. Vasseur, G. V. Mallo, H. Bodeker, B. Ritz-Laser, G. R. Dressler, M. I. Vaccaro, J. C. Dagorn, S. Moreno, and J. L. Iovanna. 2002. The HMG-I/Y-related protein p8 binds to p300 and Pax2 trans-activation domain-interacting protein to regulate the trans-activation activity of the Pax2A and Pax2B transcription factors on the glucagon gene promoter. J. Biol. Chem. 277:22314-22319.[Abstract/Free Full Text]
73
73. Hong, S., S. H. Kim, M. A. Heo, Y. H. Choi, M. J. Park, M. A. Yoo, H. D. Kim, H. S. Kang, and J. Cheong. 2004. Coactivator ASC-2 mediates heat shock factor 1-mediated transactivation dependent on heat shock. FEBS Lett. 559:165-170.[CrossRef][Medline]
74
74. Hong, W., R. J. Resnick, C. Rakowski, D. Shalloway, S. J. Taylor, and G. A. Blobel. 2002. Physical and functional interaction between the transcriptional cofactor CBP and the KH domain protein Sam68. Mol. Cancer Res. 1:48-55.[Abstract/Free Full Text]
75
75. Hsu, L. C., S. Liu, F. Abedinpour, R. D. Beech, J. M. Lahti, V. J. Kidd, J. A. Greenspan, and C. Y. Yeung. 2003. The murine G+C-rich promoter binding protein mGPBP is required for promoter-specific transcription. Mol. Cell. Biol. 23:8773-8785.[Abstract/Free Full Text]
76
76. Huang, S. M., and M. R. Stallcup. 2000. Mouse Zac1, a transcriptional coactivator and repressor for nuclear receptors. Mol. Cell. Biol. 20:1855-1867.[Abstract/Free Full Text]
77
77. Hussain, M. A., and J. F. Habener. 1999. Glucagon gene transcription activation mediated by synergistic interactions of pax-6 and cdx-2 with the p300 co-activator. J. Biol. Chem. 274:28950-28957.[Abstract/Free Full Text]
78
78. Hwang, S., Y. Gwack, H. Byun, C. Lim, and J. Choe. 2001. The Kaposi's sarcoma-associated herpesvirus K8 protein interacts with CREB-binding protein (CBP) and represses CBP-mediated transcription. J. Virol. 75:9509-9516.[Abstract/Free Full Text]
79
79. Iioka, T., K. Furukawa, A. Yamaguchi, H. Shindo, S. Yamashita, and T. Tsukazaki. 2003. P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain. J. Bone Miner. Res. 18:1419-1429.[CrossRef][Medline]
80
80. Ikeda, K., T. Stuehler, and M. Meisterernst. 2002. The H1 and H2 regions of the activation domain of herpes simplex virion protein 16 stimulate transcription through distinct molecular mechanisms. Genes Cells 7:49-58.[Abstract]
81
81. Ikeda, K., Y. Watanabe, H. Ohto, and K. Kawakami. 2002. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol. Cell. Biol. 22:6759-6766.[Abstract/Free Full Text]
82
82. Ikonen, T., J. J. Palvimo, and O. A. Janne. 1997. Interaction between the amino- and carboxyl-terminal regions of the rat androgen receptor modulates transcriptional activity and is influenced by nuclear receptor coactivators. J. Biol. Chem. 272:29821-29828.[Abstract/Free Full Text]
83
83. Iwasaki, T., W. W. Chin, and L. Ko. 2001. Identification and characterization of RRM-containing coactivator activator (CoAA) as TRBP-interacting protein, and its splice variant as a coactivator modulator (CoAM). J. Biol. Chem. 276:33375-33383.[Abstract/Free Full Text]
84
84. Jameson, S. C. 2002. Maintaining the norm: T-cell homeostasis. Nat. Rev. Immunol. 2:547-556.[Medline]
85
85. Janknecht, R., and A. Nordheim. 1996. MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. Biochem. Biophys. Res. Commun. 228:831-837.[CrossRef][Medline]
86
86. Janknecht, R., N. J. Wells, and T. Hunter. 1998. TGF-beta-stimulated cooperation of smad proteins with the coactivators CBP/p300. Genes Dev. 12:2114-2119.[Abstract/Free Full Text]
87
87. Jayaraman, G., R. Srinivas, C. Duggan, E. Ferreira, S. Swaminathan, K. Somasundaram, J. Williams, C. Hauser, M. Kurkinen, R. Dhar, S. Weitzman, G. Buttice, and B. Thimmapaya. 1999. p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter. J. Biol. Chem. 274:17342-17352.[Abstract/Free Full Text]
88
88. Ji, A., D. Dao, J. Chen, and W. R. MacLellan. 2003. EID-2, a novel member of the EID family of p300-binding proteins inhibits transactivation by MyoD. Gene 318:35-43.[CrossRef][Medline]
89
89. Jung, S. Y., A. Malovannaya, J. Wei, B. W. O'Malley, and J. Qin. 2005. Proteomic analysis of steady-state nuclear hormone receptor coactivator complexes. Mol. Endocrinol. 19:2451-2465.[Abstract/Free Full Text]
90
90. Kaida, A., Y. Ariumi, K. Baba, M. Matsubae, T. Takao, and K. Shimotohno. 2005. Identification of a novel p300-specific associating protein, phosphoribosylpyrophosphate synthetase subunit 1 (PRS 1). Biochem. J. 391:239-247.[Medline]
91
91. Kakita, T., K. Hasegawa, T. Morimoto, S. Kaburagi, H. Wada, and S. Sasayama. 1999. p300 protein as a coactivator of GATA-5 in the transcription of cardiac-restricted atrial natriuretic factor gene. J. Biol. Chem. 274:34096-34102.[Abstract/Free Full Text]
92
92. Kalkhoven, E. 2004. CBP and p300: HATs for different occasions. Biochem. Pharmacol. 68:1145-1155.[CrossRef][Medline]
93
93. Kang-Decker, N., C. Tong, F. Boussouar, D. J. Baker, W. Xu, A. A. Leontovich, W. R. Taylor, P. K. Brindle, and J. M. Van Deursen. 2004. Loss of CBP causes T cell lymphomagenesis in synergy with p27(Kip1) insufficiency. Cancer Cell 5:177-189.[CrossRef][Medline]
94
94. Karetsou, Z., A. Kretsovali, C. Murphy, O. Tsolas, and T. Papamarcaki. 2002. Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3:361-366.[CrossRef][Medline]
94
95. Kasper, L. H., F. Boussovar, K. Boyd, W. Xu, M. Biesen, J. Rehg, T. A. Baudino, J. L. Cleveland, and P. K. Brindle. 2005. Two transactivation mechanisms cooperate for the bulk of HIF-1-responsive gene expression. EMBO J. 24:3846-3858.[CrossRef][Medline]
95
96. Kasper, L. H., F. Boussouar, P. A. Ney, C. W. Jackson, J. Rehg, J. M. van Deursen, and P. K. Brindle. 2002. A transcription-factor-binding surface of coactivator p300 is required for haematopoiesis. Nature 419:738-743.[CrossRef][Medline]
96
97. Kasper, L. H., P. K. Brindle, C. A. Schnabel, C. E. J. Pritchard, M. L. Cleary, and J. M. A. van Deursen. 1999. CREB binding protein interacts with nucleoporin-specific FG repeats that activate transcription and mediate NUP98-HOXA9 oncogenicity. Mol. Cell. Biol. 19:764-776.[Abstract/Free Full Text]
97
98. Kaul, S., J. A. Blackford, Jr., J. Chen, V. V. Ogryzko, and S. S. Simons, Jr. 2000. Properties of the glucocorticoid modulatory element binding proteins GMEB-1 and -2: potential new modifiers of glucocorticoid receptor transactivation and members of the family of KDWK proteins. Mol. Endocrinol. 14:1010-1027.[Abstract/Free Full Text]
98
99. Kawamura, T., K. Ono, T. Morimoto, M. Akao, E. Iwai-Kanai, H. Wada, N. Sowa, T. Kita, and K. Hasegawa. 2004. Endothelin-1-dependent nuclear factor of activated T lymphocyte signaling associates with transcriptional coactivator p300 in the activation of the B cell leukemia-2 promoter in cardiac myocytes. Circ. Res. 94:1492-1499.[Abstract/Free Full Text]
99
100. Kennell, J. A., E. E. O'Leary, B. M. Gummow, G. D. Hammer, and O. A. MacDougald. 2003. T-cell factor 4N (TCF-4N), a novel isoform of mouse TCF-4, synergizes with beta-catenin to coactivate C/EBPalpha and steroidogenic factor 1 transcription factors. Mol. Cell. Biol. 23:5366-5375.[Abstract/Free Full Text]
100
101. Kim, J. H., E. J. Cho, S. T. Kim, and H. D. Youn. 2005. CtBP represses p300-mediated transcriptional activation by direct association with its bromodomain. Nat. Struct. Mol. Biol. 12:423-428.[CrossRef][Medline]
101
102. Kim, J. H., H. Li, and M. R. Stallcup. 2003. CoCoA, a nuclear receptor coactivator which acts through an N-terminal activation domain of p160 coactivators. Mol. Cell 12:1537-1549.[CrossRef][Medline]
102
103. Kim, R. H., K. C. Flanders, S. Birkey Reffey, L. A. Anderson, C. S. Duckett, N. D. Perkins, and A. B. Roberts. 2001. SNIP1 inhibits NF-kappa B signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional co-activators. J. Biol. Chem. 276:46297-46304.[Abstract/Free Full Text]
103
104. Kishikawa, S., T. Murata, H. Kimura, K. Shiota, and K. K. Yokoyama. 2002. Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger proteins. Eur. J. Biochem. 269:2961-2970.[Medline]
104
105. Ko, L., G. R. Cardona, and W. W. Chin. 2000. Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator. Proc. Natl. Acad. Sci. USA 97:6212-6217.[Abstract/Free Full Text]
105
106. Kobayashi, A., K. Numayama-Tsuruta, K. Sogawa, and Y. Fujii-Kuriyama. 1997. CBP/p300 functions as a possible transcriptional coactivator of Ah receptor nuclear translocator (Arnt). J. Biochem. (Tokyo) 122:703-710.[Abstract/Free Full Text]
106
107. Kovacs, K. A., M. Steinmann, P. J. Magistretti, O. Halfon, and J. R. Cardinaux. 2003. CCAAT/enhancer-binding protein family members recruit the coactivator CREB-binding protein and trigger its phosphorylation. J. Biol. Chem. 278:36959-36965.[Abstract/Free Full Text]
107
108. Koyanagi, M., M. Hijikata, K. Watashi, O. Masui, and K. Shimotohno. 2005. Centrosomal P4.1-associated protein is a new member of transcriptional coactivators for nuclear factor-kappaB. J. Biol. Chem. 280:12430-12437.[Abstract/Free Full Text]
108
109. Kumar, B. R., V. Swaminathan, S. Banerjee, and T. K. Kundu. 2001. p300-mediated acetylation of human transcriptional coactivator PC4 is inhibited by phosphorylation. J. Biol. Chem. 276:16804-16809.[Abstract/Free Full Text]
109
110. Kung, A. L., V. I. Rebel, R. T. Bronson, L. E. Ch'ng, C. A. Sieff, D. M. Livingston, and T. P. Yao. 2000. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Dev. 14:272-277.[Abstract/Free Full Text]
110
111. Kwon, H. S., B. Huang, T. G. Unterman, and R. A. Harris. 2004. Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 gene induction by dexamethasone through inactivation of FOXO transcription factors. Diabetes 53:899-910.[Abstract/Free Full Text]
111
112. Labalette, C., C. A. Renard, C. Neuveut, M. A. Buendia, and Y. Wei. 2004. Interaction and functional cooperation between the LIM protein FHL2, CBP/p300, and ß-catenin. Mol. Cell. Biol. 24:10689-10702.[Abstract/Free Full Text]
112
113. Lamprecht, C., and C. R. Mueller. 1999. D-site binding protein transactivation requires the proline- and acid-rich domain and involves the coactivator p300. J. Biol. Chem. 274:17643-17648.[Abstract/Free Full Text]
113
114. Lau, P., P. Bailey, D. H. Dowhan, and G. E. Muscat. 1999. Exogenous expression of a dominant negative RORalpha1 vector in muscle cells impairs differentiation: RORalpha1 directly interacts with p300 and myoD. Nucleic Acids Res. 27:411-420.[Abstract/Free Full Text]
114
115. Laurance, M. E., R. P. Kwok, M. S. Huang, J. P. Richards, J. R. Lundblad, and R. H. Goodman. 1997. Differential activation of viral and cellular promoters by human T-cell lymphotropic virus-1 tax and cAMP-responsive element modulator isoforms. J. Biol. Chem. 272:2646-2651.[Abstract/Free Full Text]
115
116. Legube, G., and D. Trouche. 2003. Regulating histone acetyltransferases and deacetylases. EMBO Rep. 4:944-947.[CrossRef][Medline]
116
117. Leong, G. M., N. Subramaniam, L. L. Issa, J. B. Barry, T. Kino, P. H. Driggers, M. J. Hayman, J. A. Eisman, and E. M. Gardiner. 2004. Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. Biochem. Biophys. Res. Commun. 315:1070-1076.[CrossRef][Medline]
117
118. Li, M., G. Pascual, and C. K. Glass. 2000. Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene. Mol. Cell. Biol. 20:4699-4707.[Abstract/Free Full Text]
118
119. Li, S., C. M. Armstrong, N. Bertin, H. Ge, S. Milstein, M. Boxem, P. O. Vidalain, J. D. Han, A. Chesneau, T. Hao, D. S. Goldberg, N. Li, M. Martinez, J. F. Rual, P. Lamesch, L. Xu, M. Tewari, S. L. Wong, L. V. Zhang, G. F. Berriz, L. Jacotot, P. Vaglio, J. Reboul, T. Hirozane-Kishikawa, Q. Li, H. W. Gabel, A. Elewa, B. Baumgartner, D. J. Rose, H. Yu, S. Bosak, R. Sequerra, A. Fraser, S. E. Mango, W. M. Saxton, S. Strome, S. Van Den Heuvel, F. Piano, J. Vandenhaute, C. Sardet, M. Gerstein, L. Doucette-Stamm, K. C. Gunsalus, J. W. Harper, M. E. Cusick, F. P. Roth, D. E. Hill, and M. Vidal. 2004. A map of the interactome network of the metazoan C. elegans. Science 303:540-543.[Abstract/Free Full Text]
119
120. Li, S., B. Aufiero, R. L. Schiltz, and M. J. Walsh. 2000. Regulation of the homeodomain CCAAT displacement/cut protein function by histone acetyltransferases p300/CREB-binding protein (CBP)-associated factor and CBP. Proc. Natl. Acad. Sci. USA 97:7166-7171.[Abstract/Free Full Text]
120
121. Liu, Y., G. L. Borchert, and J. M. Phang. 2004. Polyoma enhancer activator 3, an ets transcription factor, mediates the induction of cyclooxygenase-2 by nitric oxide in colorectal cancer cells. J. Biol. Chem. 279:18694-18700.[Abstract/Free Full Text]
121
122. Long, J., G. Wang, I. Matsuura, D. He, and F. Liu. 2004. Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3). Proc. Natl. Acad. Sci. USA 101:99-104.[Abstract/Free Full Text]
122
123. Ma, Z. Q., Z. Liu, E. S. Ngan, and S. Y. Tsai. 2001. Cdc25B functions as a novel coactivator for the steroid receptors. Mol. Cell. Biol. 21:8056-8067.[Abstract/Free Full Text]
123
124. MacLellan, W. R., G. Xiao, M. Abdellatif, and M. D. Schneider. 2000. A novel Rb- and p300-binding protein inhibits transactivation by MyoD. Mol. Cell. Biol. 20:8903-8915.[Abstract/Free Full Text]
124
125. Macpartlin, M., S. X. Zeng, H. Lee, D. Stauffer, Y. Jin, M. Thayer, and H. Lu. 2005. p300 regulates p63 transcriptional activity. J. Biol. Chem. 280:30604-30610.[Abstract/Free Full Text]
125
126. Mahmud, D. L., M. G-Amlak, D. K. Deb, L. C. Platanias, S. Uddin, and A. Wickrema. 2002. Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells. Oncogene 21:1556-1562.[CrossRef][Medline]
126
127. Major, M. L., R. Lepe, and R. H. Costa. 2004. Forkhead box M1B transcriptional activity requires binding of Cdk-cyclin complexes for phosphorylation-dependent recruitment of p300/CBP coactivators. Mol. Cell. Biol. 24:2649-2661.[Abstract/Free Full Text]
127
128. Mandolesi, G., S. Gargano, M. Pennuto, B. Illi, R. Molfetta, L. Soucek, L. Mosca, A. Levi, R. Jucker, and S. Nasi. 2002. NGF-dependent and tissue-specific transcription of vgf is regulated by a CREB-p300 and bHLH factor interaction. FEBS Lett. 510:50-56.[CrossRef][Medline]
128
129. Marambaud, P., P. H. Wen, A. Dutt, J. Shioi, A. Takashima, R. Siman, and N. K. Robakis. 2003. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 114:635-645.[CrossRef][Medline]
129
130. Masumi, A., and K. Ozato. 2001. Coactivator p300 acetylates the interferon regulatory factor-2 in U937 cells following phorbol ester treatment. J. Biol. Chem. 276:20973-20980.[Abstract/Free Full Text]
130
131. Mathew, S., E. Mascareno, and M. A. Siddiqui. 2004. A ternary complex of transcription factors, Nished and NFATc4, and co-activator p300 bound to an intronic sequence, intronic regulatory element, is pivotal for the up-regulation of myosin light chain-2v gene in cardiac hypertrophy. J. Biol. Chem. 279:41018-41027.[Abstract/Free Full Text]
131
132. Matt, T., M. A. Martinez-Yamout, H. J. Dyson, and P. E. Wright. 2004. The CBP/p300 TAZ1 domain in its native state is not a binding partner of MDM2. Biochem. J. 381:685-691.[CrossRef][Medline]
132
133. McManus, K. J., and M. J. Hendzel. 2001. CBP, a transcriptional coactivator and acetyltransferase. Biochem. Cell Biol. 79:253-266.[CrossRef][Medline]
133
134. Mehra-Chaudhary, R., H. Matsui, and R. Raghow. 2001. Msx3 protein recruits histone deacetylase to down-regulate the Msx1 promoter. Biochem. J. 353:13-22.[Medline]
134
135. Messina, D. N., J. Glasscock, W. Gish, and M. Lovett. 2004. An ORFeome-based analysis of human transcription factor genes and the construction of a microarray to interrogate their expression. Genome Res. 14:2041-2047.[Abstract/Free Full Text]
135
136. Meyers, E. N., M. Lewandoski, and G. R. Martin. 1998. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat. Genet. 18:136-141.[CrossRef][Medline]
136
137. Misra, P., C. Qi, S. Yu, S. H. Shah, W. Q. Cao, M. S. Rao, B. Thimmapaya, Y. Zhu, and J. K. Reddy. 2002. Interaction of PIMT with transcriptional coactivators CBP, p300, and PBP differential role in transcriptional regulation. J. Biol. Chem. 277:20011-20019.[Abstract/Free Full Text]
137
138. Mizukami, J., and T. Taniguchi. 1997. The antidiabetic agent thiazolidinedione stimulates the interaction between PPAR gamma and CBP. Biochem. Biophys. Res. Commun. 240:61-64.[CrossRef][Medline]
138
139. Molinari, S., F. Relaix, M. Lemonnier, B. Kirschbaum, B. Schafer, and M. Buckingham. 2004. A novel complex regulates cardiac actin gene expression through interaction of Emb, a class VI POU domain protein, MEF2D, and the histone transacetylase p300. Mol. Cell. Biol. 24:2944-2957.[Abstract/Free Full Text]
139
140. Monroy, M. A., D. D. Ruhl, X. Xu, D. K. Granner, P. Yaciuk, and J. C. Chrivia. 2001. Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP. J. Biol. Chem. 276:40721-40726.[Abstract/Free Full Text]
140
141. Morris, L., K. E. Allen, and N. B. La Thangue. 2000. Regulation of E2F transcription by cyclin E-Cdk2 kinase mediated through p300/CBP co-activators. Nat. Cell. Biol. 2:232-239.[CrossRef][Medline]
141
142. Murray, P. J., L. Wang, C. Onufryk, R. I. Tepper, and R. A. Young. 1997. T cell-derived IL-10 antagonizes macrophage function in mycobacterial infection. J. Immunol. 158:315-321.[Abstract]
142
143. Nakashima, K., M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune, M. Kawabata, K. Miyazono, and T. Taga. 1999. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 284:479-482.[Abstract/Free Full Text]
143
144. Novak, A., C. Guo, W. Yang, A. Nagy, and C. G. Lobe. 2000. Z/EG, a double reporter mouse line that expresses enhanced green fluorescent protein upon Cre-mediated excision. Genesis 28:147-155.[CrossRef][Medline]
144
145. Nowling, T. K., L. R. Johnson, M. S. Wiebe, and A. Rizzino. 2000. Identification of the transactivation domain of the transcription factor Sox-2 and an associated co-activator. J. Biol. Chem. 275:3810-3818.[Abstract/Free Full Text]
145
146. Nucifora, F. C., Jr., M. Sasaki, M. F. Peters, H. Huang, J. K. Cooper, M. Yamada, H. Takahashi, S. Tsuji, J. Troncoso, V. L. Dawson, T. M. Dawson, and C. A. Ross. 2001. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 291:2423-2428.[Abstract/Free Full Text]
146
147. Ohshima, T., E. Yoshida, T. Nakajima, K. I. Yagami, and A. Fukamizu. 2001. Effects of interaction between parvovirus minute virus of mice NS1 and coactivator CBP on NS1- and p53-transactivation. Int. J. Mol. Med. 7:49-54.[Medline]
147
148. O'Sullivan, A., H. C. Chang, Q. Yu, and M. H. Kaplan. 2004. STAT4 is required for interleukin-12-induced chromatin remodeling of the CD25 locus. J. Biol. Chem. 279:7339-7345.[Abstract/Free Full Text]
148
149. Oswald, F., B. Tauber, T. Dobner, S. Bourteele, U. Kostezka, G. Adler, S. Liptay, and R. M. Schmid. 2001. p300 acts as a transcriptional coactivator for mammalian Notch-1. Mol. Cell. Biol. 21:7761-7774.[Abstract/Free Full Text]
149
150. Pan, J., C. Jin, T. Murata, and K. K. Yokoyama. 2003. Sequence specific transcription factor, JDP2 interacts with histone and inhibits p300-mediated histone acetylation. Nucleic Acids Res. Suppl. 2003:305-306.
150
151. Papoutsopoulou, S., and R. Janknecht. 2000. Phosphorylation of ETS transcription factor ER81 in a complex with its coactivators CREB-binding protein and p300. Mol. Cell. Biol. 20:7300-7310.[Abstract/Free Full Text]
151
152. Park, S. R., E. K. Lee, B. C. Kim, and P. H. Kim. 2003. p300 cooperates with Smad3/4 and Runx3 in TGFbeta1-induced IgA isotype expression. Eur. J. Immunol. 33:3386-3392.[CrossRef][Medline]
152
153. Pauleau, A. L., R. Rutschman, R. Lang, A. Pernis, S. S. Watowich, and P. J. Murray. 2004. Enhancer-mediated control of macrophage-specific arginase I expression. J. Immunol. 172:7565-7573.[Abstract/Free Full Text]
153
154. Pedeux, R., S. Sengupta, J. C. Shen, O. N. Demidov, S. Saito, H. Onogi, K. Kumamoto, S. Wincovitch, S. H. Garfield, M. McMenamin, M. Nagashima, S. R. Grossman, E. Appella, and C. C. Harris. 2005. ING2 regulates the onset of replicative senescence by induction of p300-dependent p53 acetylation. Mol. Cell. Biol. 25:6639-6648.[Abstract/Free Full Text]
154
155. Pelletier, G., V. Y. Stefanovsky, M. Faubladier, I. Hirschler-Laszkiewicz, J. Savard, L. I. Rothblum, J. Cote, and T. Moss. 2000. Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription. Mol. Cell 6:1059-1066.[CrossRef][Medline]
155
156. Peng, Y. C., D. E. Breiding, F. Sverdrup, J. Richard, and E. J. Androphy. 2000. AMF-1/Gps2 binds p300 and enhances its interaction with papillomavirus E2 proteins. J. Virol. 74:5872-5879.[Abstract/Free Full Text]
156
157. Perkins, N. D., L. K. Felzien, J. C. Betts, K. Leung, D. H. Beach, and G. J. Nabel. 1997. Regulation of NF-kappaB by cyclin-dependent kinases associated with the p300 coactivator. Science 275:523-527.[Abstract/Free Full Text]
157
158. Pfitzner, E., R. Jahne, M. Wissler, E. Stoecklin, and B. Groner. 1998. p300/CREB-binding protein enhances the prolactin-mediated transcriptional induction through direct interaction with the transactivation domain of Stat5, but does not participate in the Stat5- mediated suppression of the glucocorticoid response. Mol. Endocrinol. 12:1582-1593.[Abstract/Free Full Text]
158
159. Phan, H. M., A. W. Xu, C. Coco, G. Srajer, S. Wyszomierski, Y. A. Evrard, R. Eckner, and S. Y. Dent. 2005. GCN5 and p300 share essential functions during early embryogenesis. Dev. Dyn. 233:1337-1347.[CrossRef][Medline]
159
160. Pitkanen, J., V. Doucas, T. Sternsdorf, T. Nakajima, S. Aratani, K. Jensen, H. Will, P. Vahamurto, J. Ollila, M. Vihinen, H. S. Scott, S. E. Antonarakis, J. Kudoh, N. Shimizu, K. Krohn, and P. Peterson. 2000. The autoimmune regulator protein has transcriptional transactivating properties and interacts with the common coactivator CREB-binding protein. J. Biol. Chem. 275:16802-16809.[Abstract/Free Full Text]
160
161. Postigo, A. A., J. L. Depp, J. J. Taylor, and K. L. Kroll. 2003. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J. 22:2453-2462.[CrossRef][Medline]
161
162. Qiu, Y., M. Guo, S. Huang, and R. Stein. 2002. Insulin gene transcription is mediated by interactions between the p300 coactivator and PDX-1, BETA2, and E47. Mol. Cell. Biol. 22:412-420.[Abstract/Free Full Text]
162
163. Ramirez, S., S. Ait-Si-Ali, P. Robin, D. Trouche, A. Harel-Bellan, and S. Ait Si Ali. 1997. The CREB-binding protein (CBP) cooperates with the serum response factor for transactivation of the c-fos serum response element. J. Biol. Chem. 272:31016-31021.[Abstract/Free Full Text]
163
164. Rausa, F. M., Y. Tan, and R. H. Costa. 2003. Association between hepatocyte nuclear factor 6 (HNF-6) and FoxA2 DNA binding domains stimulates FoxA2 transcriptional activity but inhibits HNF-6 DNA binding. Mol. Cell. Biol. 23:437-449.[Abstract/Free Full Text]
164
165. Rebel, V. I., A. L. Kung, E. A. Tanner, H. Yang, R. T. Bronson, and D. M. Livingston. 2002. Distinct roles for CREB-binding protein and p300 in hematopoietic stem cell self-renewal. Proc. Natl. Acad. Sci. USA 99:14789-14794.[Abstract/Free Full Text]
165
166. Rossow, K. L., and R. Janknecht. 2001. The Ewing's sarcoma gene product functions as a transcriptional activator. Cancer Res. 61:2690-2695.[Abstract/Free Full Text]
166
167. Rossow, K. L., and R. Janknecht. 2003. Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300. Oncogene 22:151-156.[CrossRef][Medline]
167
168. Sartorelli, V., J. Huang, Y. Hamamori, and L. Kedes. 1997. Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C. Mol. Cell. Biol. 17:1010-1026.[Abstract]
168
169. See, R. H., D. Calvo, Y. Shi, H. Kawa, M. P. Luke, and Z. Yuan. 2001. Stimulation of p300-mediated transcription by the kinase MEKK1. J. Biol. Chem. 276:16310-16317.[Abstract/Free Full Text]
169
170. Seibler, J., D. Schubeler, S. Fiering, M. Groudine, and J. Bode. 1998. DNA cassette exchange in ES cells mediated by Flp recombinase: an efficient strategy for repeated modification of tagged loci by marker-free constructs. Biochemistry 37:6229-6234.[CrossRef][Medline]
170
171. SenBanerjee, S., Z. Lin, G. B. Atkins, D. M. Greif, R. M. Rao, A. Kumar, M. W. Feinberg, Z. Chen, D. I. Simon, F. W. Luscinskas, T. M. Michel, M. A. Gimbrone, Jr., G. Garcia-Cardena, and M. K. Jain. 2004. KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation. J. Exp. Med. 199:1305-1315.[Abstract/Free Full Text]
171
172. Shen, G., V. Hebbar, S. Nair, C. Xu, W. Li, W. Lin, Y. S. Keum, J. Han, M. A. Gallo, and A. N. Kong. 2004. Regulation of Nrf2 transactivation domain activity. The differential effects of mitogen-activated protein kinase cascades and synergistic stimulatory effect of Raf and CREB-binding protein. J. Biol. Chem. 279:23052-23060.[Abstract/Free Full Text]
172
173. Shen, W. F., K. Krishnan, H. J. Lawrence, and C. Largman. 2001. The HOX homeodomain proteins block CBP histone acetyltransferase activity. Mol. Cell. Biol. 21:7509-7522.[Abstract/Free Full Text]
173
174. Shetty, S., T. Takahashi, H. Matsui, R. Ayengar, and R. Raghow. 1999. Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300). Biochem. J. 339:751-758.[CrossRef][Medline]
174
175. Shibanuma, M., J. R. Kim-Kaneyama, S. Sato, and K. Nose. 2004. A LIM protein, Hic-5, functions as a potential coactivator for Sp1. J. Cell. Biochem. 91:633-645.[CrossRef][Medline]
175
176. Shikama, N., H. M. Chan, M. Krstic-Demonacos, L. Smith, C. W. Lee, W. Cairns, and N. B. La Thangue. 2000. Functional interaction between nucleosome assembly proteins and p300/CREB-binding protein family coactivators. Mol. Cell. Biol. 20:8933-8943.[Abstract/Free Full Text]
176
177. Shikama, N., W. Lutz, R. Kretzschmar, N. Sauter, J. F. Roth, S. Marino, J. Wittwer, A. Scheidweiler, and R. Eckner. 2003. Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. EMBO J. 22:5175-5185.[CrossRef][Medline]
177
178. Shiseki, M., M. Nagashima, R. M. Pedeux, M. Kitahama-Shiseki, K. Miura, S. Okamura, H. Onogi, Y. Higashimoto, E. Appella, J. Yokota, and C. C. Harris. 2003. p29ING4 and p28ING5 bind to p53 and p300, and enhance p53 activity. Cancer Res. 63:2373-2378.[Abstract/Free Full Text]
178
179. Sierra, J., A. Villagra, R. Paredes, F. Cruzat, S. Gutierrez, A. Javed, G. Arriagada, J. Olate, M. Imschenetzky, A. J. Van Wijnen, J. B. Lian, G. S. Stein, J. L. Stein, and M. Montecino. 2003. Regulation of the bone-specific osteocalcin gene by p300 requires Runx2/Cbfa1 and the vitamin D3 receptor but not p300 intrinsic histone acetyltransferase activity. Mol. Cell. Biol. 23:3339-3351.[Abstract/Free Full Text]
179
180. Simone, C., P. Stiegler, S. V. Forcales, L. Bagella, A. De Luca, V. Sartorelli, A. Giordano, and P. L. Puri. 2004. Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300. Oncogene 23:2177-2187.[CrossRef][Medline]
180
181. Slepak, T. I., K. A. Webster, J. Zang, H. Prentice, A. O'Dowd, M. N. Hicks, and N. H. Bishopric. 2001. Control of cardiac-specific transcription by p300 through myocyte enhancer factor-2D. J. Biol. Chem. 276:7575-7585.[Abstract/Free Full Text]
181
182. Smit, D. J., A. G. Smith, P. G. Parsons, G. E. Muscat, and R. A. Sturm. 2000. Domains of Brn-2 that mediate homodimerization and interaction with general and melanocytic transcription factors. Eur. J. Biochem. 267:6413-6422.[Medline]
182
183. Song, C. Z., K. Keller, K. Murata, H. Asano, and G. Stamatoyannopoulos. 2002. Functional interaction between coactivators CBP/p300, PCAF, and transcription factor FKLF2. J. Biol. Chem. 277:7029-7036.[Abstract/Free Full Text]
183
184. Steffan, J. S., A. Kazantsev, O. Spasic-Boskovic, M. Greenwald, Y. Z. Zhu, H. Gohler, E. E. Wanker, G. P. Bates, D. E. Housman, and L. M. Thompson. 2000. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 97:6763-6768.[Abstract/Free Full Text]
184
185. Sterner, D. E., and S. L. Berger. 2000. Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64:435-459.[Abstract/Free Full Text]
185
186. Strano, S., O. Monti, N. Pediconi, A. Baccarini, G. Fontemaggi, E. Lapi, F. Mantovani, A. Damalas, G. Citro, A. Sacchi, G. Del Sal, M. Levrero, and G. Blandino. 2005. The transcriptional coactivator Yes-associated protein drives p73 gene-target specificity in response to DNA damage. Mol. Cell 18:447-459.[CrossRef][Medline]
186
187. Sugihara, T. M., E. I. Kudryavtseva, V. Kumar, J. J. Horridge, and B. Andersen. 2001. The POU domain factor Skin-1a represses the keratin 14 promoter independent of DNA binding. A possible role for interactions between Skn-1a and CREB-binding protein/p300. J. Biol. Chem. 276:33036-33044.[Abstract/Free Full Text]
187
188. Sun, Z., J. Pan, W. X. Hope, S. N. Cohen, and S. P. Balk. 1999. Tumor susceptibility gene 101 protein represses androgen receptor transactivation and interacts with p300. Cancer 86:689-696.[CrossRef][Medline]
188
189. Swenson, J. J., E. Holley-Guthrie, and S. C. Kenney. 2001. Epstein-Barr virus immediate-early protein BRLF1 interacts with CBP, promoting enhanced BRLF1 transactivation. J. Virol. 75:6228-6234.[Abstract/Free Full Text]
189
190. Takemaru, K. I., and R. T. Moon. 2000. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J. Cell Biol. 149:249-254.[Abstract/Free Full Text]
190
191. Tanaka, Y., I. Naruse, T. Maekawa, H. Masuya, T. Shiroishi, and S. Ishii. 1997. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome. Proc. Natl. Acad. Sci. USA 94:10215-10220.[Abstract/Free Full Text]
191
192. Tatematsu, K., N. Yoshimoto, T. Koyanagi, C. Tokunaga, T. Tachibana, Y. Yoneda, M. Yoshida, T. Okajima, K. Tanizawa, and S. Kuroda. 2005. Nuclear-cytoplasmic shuttling of a RING-IBR protein RBCK1 and its functional interaction with nuclear body proteins. J. Biol. Chem. 280:22937-22944.[Abstract/Free Full Text]
192
193. Tini, M., A. Benecke, S. J. Um, J. Torchia, R. M. Evans, and P. Chambon. 2002. Association of CBP/p300 acetylase and thymine DNA glycosylase links DNA repair and transcription. Mol. Cell 9:265-277.[CrossRef][Medline]
193
194. Tohkin, M., M. Fukuhara, G. Elizondo, S. Tomita, and F. J. Gonzalez. 2000. Aryl hydrocarbon receptor is required for p300-mediated induction of DNA synthesis by adenovirus E1A. Mol. Pharmacol. 58:845-851.[Abstract/Free Full Text]
194
195. Topper, J. N., M. R. DiChiara, J. D. Brown, A. J. Williams, D. Falb, T. Collins, and M. A. Gimbrone, Jr. 1998. CREB binding protein is a required coactivator for Smad-dependent, transforming growth factor beta transcriptional responses in endothelial cells. Proc. Natl. Acad. Sci. USA 95:9506-9511.[Abstract/Free Full Text]
195
196. Toyama, T., and H. Iwase. 2004. p33ING1b and estrogen receptor (ER) alpha. Breast Cancer 11:33-37.[Medline]
196
197. Tsuda, M., S. Takahashi, Y. Takahashi, and H. Asahara. 2003. Transcriptional co-activators CREB-binding protein and p300 regulate chondrocyte-specific gene expression via association with Sox9. J. Biol. Chem. 278:27224-27229.[Abstract/Free Full Text]
197
198. Vadlamudi, R. K., R. A. Wang, A. Mazumdar, Y. Kim, J. Shin, A. Sahin, and R. Kumar. 2001. Molecular cloning and characterization of PELP1, a novel human coregulator of estrogen receptor alpha. J. Biol. Chem. 276:38272-38279.[Abstract/Free Full Text]
198
199. Valineva, T., J. Yang, R. Palovuori, and O. Silvennoinen. 2005. The transcriptional co-activator protein p100 recruits histone acetyltransferase activity to STAT6 and mediates interaction between the CREB-binding protein and STAT6. J. Biol. Chem. 280:14989-14996.[Abstract/Free Full Text]
199
200. van der Horst, A., L. G. Tertoolen, L. M. de Vries-Smits, R. A. Frye, R. H. Medema, and B. M. Burgering. 2004. FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J. Biol. Chem. 279:28873-28879.[Abstract/Free Full Text]
200
201. van Wely, K. H., A. C. Molijn, A. Buijs, M. A. Meester-Smoor, A. J. Aarnoudse, A. Hellemons, P. den Besten, G. C. Grosveld, and E. C. Zwarthoff. 2003. The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription. Oncogene 22:699-709.[CrossRef][Medline]
201
202. Verma, U. N., Y. Yamamoto, S. Prajapati, and R. B. Gaynor. 2004. Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression. J. Biol. Chem. 279:3509-3515.[Abstract/Free Full Text]
202
203. Vervoorts, J., J. M. Luscher-Firzlaff, S. Rottmann, R. Lilischkis, G. Walsemann, K. Dohmann, M. Austen, and B. Luscher. 2003. Stimulation of c-MYC transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Rep. 4:484-490.[CrossRef][Medline]
203
204. Vo, N. K., and R. H. Goodman. 2001. CBP and p300 in transcriptional regulation. J. Biol. Chem. 276:13505-13508.[Free Full Text]
204
205. Voegel, J. J., M. J. Heine, M. Tini, V. Vivat, P. Chambon, and H. Gronemeyer. 1998. The coactivator TIF2 contains three nuclear receptor-binding motifs and mediates transactivation through CBP binding-dependent and -independent pathways. EMBO J. 17:507-519.[CrossRef][Medline]
205
206. Wada, H., K. Hasegawa, T. Morimoto, T. Kakita, T. Yanazume, and S. Sasayama. 2000. A p300 protein as a coactivator of GATA-6 in the transcription of the smooth muscle-myosin heavy chain gene. J. Biol. Chem. 275:25330-25335.[Abstract/Free Full Text]
206
207. Wallberg, A. E., S. Yamamura, S. Malik, B. M. Spiegelman, and R. G. Roeder. 2003. Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1alpha. Mol. Cell 12:1137-1149.[CrossRef][Medline]
207
208. Wang, A., T. Ikura, K. Eto, and M. S. Ota. 2004. Dynamic interaction of p220(NPAT) and CBP/p300 promotes S-phase entry. Biochem. Biophys. Res. Commun. 325:1509-1516.[CrossRef][Medline]
208
209. Wang, H., R. Fang, J. Y. Cho, T. A. Libermann, and P. Oettgen. 2004. Positive and negative modulation of the transcriptional activity of the ETS factor ESE-1 through interaction with p300, CREB-binding protein, and Ku 70/86. J. Biol. Chem. 279:25241-25250.[Abstract/Free Full Text]
209
210. Wang, W., S. B. Lee, R. Palmer, L. W. Ellisen, and D. A. Haber. 2001. A functional interaction with CBP contributes to transcriptional activation by the Wilms tumor suppressor WT1. J. Biol. Chem. 276:16810-16816.[Abstract/Free Full Text]
210
211. Wansa, K. D., J. M. Harris, and G. E. Muscat. 2002. The activation function-1 domain of Nur77/NR4A1 mediates trans-activation, cell specificity, and coactivator recruitment. J. Biol. Chem. 277:33001-33011.[Abstract/Free Full Text]
211
212. Weaver, B. K., K. P. Kumar, and N. C. Reich. 1998. Interferon regulatory factor 3 and CREB-binding protein/p300 are subunits of double-stranded RNA-activated transcription factor DRAF1. Mol. Cell. Biol. 18:1359-1368.[Abstract/Free Full Text]
212
213. Wherry, E. J., and R. Ahmed. 2004. Memory CD8 T-cell differentiation during viral infection. J. Virol. 78:5535-5545.[Free Full Text]
213
214. Williams, C. J., T. Naito, P. G. Arco, J. R. Seavitt, S. M. Cashman, B. De Souza, X. Qi, P. Keables, U. H. Von Andrian, and K. Georgopoulos. 2004. The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development. Immunity 20:719-733.[CrossRef][Medline]
214
215. Wu, L., J. Liu, P. Gao, M. Nakamura, Y. Cao, H. Shen, and J. D. Griffin. 2005. Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. EMBO J. 24:2391-2402.[CrossRef][Medline]
215
216. Xu, W., H. Chen, K. Du, H. Asahara, M. Tini, B. M. Emerson, M. Montminy, and R. M. Evans. 2001. A transcriptional switch mediated by cofactor methylation. Science 294:2507-2511.[Abstract/Free Full Text]
216
217. Yahata, T., M. P. de Caestecker, R. J. Lechleider, S. Andriole, A. B. Roberts, K. J. Isselbacher, and T. Shioda. 2000. The MSG1 non-DNA-binding transactivator binds to the p300/CBP coactivators, enhancing their functional link to the Smad transcription factors. J. Biol. Chem. 275:8825-8834.[Abstract/Free Full Text]
217
218. Yamamoto, H., F. Kihara-Negishi, T. Yamada, M. Suzuki, T. Nakano, and T. Oikawa. 2002. Interaction between the hematopoietic Ets transcription factor Spi-B and the coactivator CREB-binding protein associated with negative cross-talk with c-Myb. Cell Growth Differ. 13:69-75.[Abstract/Free Full Text]
218
219. Yamamoto, Y., U. N. Verma, S. Prajapati, Y. T. Kwak, and R. B. Gaynor. 2003. Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression. Nature 423:655-659.[CrossRef][Medline]
219
220. Yanagi, Y., Y. Masuhiro, M. Mori, J. Yanagisawa, and S. Kato. 2000. p300/CBP acts as a coactivator of the cone-rod homeobox transcription factor. Biochem. Biophys. Res. Commun. 269:410-414.[CrossRef][Medline]
220
221. Yang, C., L. H. Shapiro, M. Rivera, A. Kumar, and P. K. Brindle. 1998. A role for CREB binding protein and p300 transcriptional coactivators in Ets-1 transactivation functions. Mol. Cell. Biol. 18:2218-2229.[Abstract/Free Full Text]
221
222. Yang, H., C. H. Lin, G. Ma, M. O. Baffi, and M. G. Wathelet. 2003. Interferon regulatory factor-7 synergizes with other transcription factors through multiple interactions with p300/CBP coactivators. J. Biol. Chem. 278:15495-15504.[Abstract/Free Full Text]
222
223. Yang, T., R. J. Davis, and C. W. Chow. 2001. Requirement of two NFATc4 transactivation domains for CBP potentiation. J. Biol. Chem. 276:39569-39576.[Abstract/Free Full Text]
223
224. Yao, T. P., S. P. Oh, M. Fuchs, N. D. Zhou, L. E. Ch'ng, D. Newsome, R. T. Bronson, E. Li, D. M. Livingston, and R. Eckner. 1998. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 93:361-372.[CrossRef][Medline]
224
225. Yi, M., G. X. Tong, B. Murry, and C. R. Mendelson. 2002. Role of CBP/p300 and SRC-1 in transcriptional regulation of the pulmonary surfactant protein-A (SP-A) gene by thyroid transcription factor-1 (TTF-1). J. Biol. Chem. 277:2997-3005.[Abstract/Free Full Text]
225
226. Yin, X., D. R. Warner, E. A. Roberts, M. M. Pisano, and R. M. Greene. 2005. Identification of novel CBP interacting proteins in embryonic orofacial tissue. Biochem. Biophys. Res. Commun. 329:1010-1017.[Medline]
226
227. Yin, X., D. R. Warner, E. A. Roberts, M. M. Pisano, and R. M. Greene. 2005. Novel interaction between nuclear co-activator CBP and the CDK5 activator binding protein-C53. Int. J. Mol. Med. 16:251-256.[Medline]
227
228. Yin, X., D. R. Warner, E. A. Roberts, M. M. Pisano, and R. M. Greene. 2005. Novel interaction between nuclear coactivator CBP and the protein inhibitor of activated Stat1 (PIAS1). J. Interferon Cytokine Res. 25:321-327.[Medline]
228
229. Yu, C. T., M. H. Feng, H. M. Shih, and M. Z. Lai. 2002. Increased p300 expression inhibits glucocorticoid receptor-T-cell receptor antagonism but does not affect thymocyte positive selection. Mol. Cell. Biol. 22:4556-4566.[Abstract/Free Full Text]
229
230. Zhang, W., J. W. Nisbet, B. Albrecht, W. Ding, F. Kashanchi, J. T. Bartoe, and M. D. Lairmore. 2001. Hum. T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein/p300. J. Virol. 75:9885-9895.[Abstract/Free Full Text]
230
231. Zhang, Z., and C. T. Teng. 2003. Phosphorylation of Kruppel-like factor 5 (KLF5/IKLF) at the CBP interaction region enhances its transactivation function. Nucleic Acids Res. 31:2196-2208.[Abstract/Free Full Text]
231
232. Zhao, F., R. McCarrick-Walmsley, P. Akerblad, M. Sigvardsson, and T. Kadesch. 2003. Inhibition of p300/CBP by early B-cell factor. Mol. Cell. Biol. 23:3837-3846.[Abstract/Free Full Text]
232
233. Zhu, Q., G. Wani, M. A. Wani, and A. A. Wani. 2001. Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP-responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53. Cancer Res. 61:64-70.[Abstract/Free Full Text]

---

Molecular and Cellular Biology, February 2006, p. 789-809, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.789-809.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Byun, J. S., Wong, M. M., Cui, W., Idelman, G., Li, Q., De Siervi, A., Bilke, S., Haggerty, C. M., Player, A., Wang, Y. H., Thirman, M. J., Kaberlein, J. J., Petrovas, C., Koup, R. A., Longo, D., Ozato, K., Gardner, K. (2009). Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes. Proc. Natl. Acad. Sci. USA 106: 19286-19291 [Abstract] [Full Text]  
• Fukuyama, T., Kasper, L. H., Boussouar, F., Jeevan, T., van Deursen, J., Brindle, P. K. (2009). Histone Acetyltransferase CBP Is Vital To Demarcate Conventional and Innate CD8+ T-Cell Development. Mol. Cell. Biol. 29: 3894-3904 [Abstract] [Full Text]  
• Hilton, D. J., Kile, B. T., Alexander, W. S. (2009). Mutational inhibition of c-Myb or p300 ameliorates treatment-induced thrombocytopenia. Blood 113: 5599-5604 [Abstract] [Full Text]  
• Gomez, R. A., Pentz, E. S., Jin, X., Cordaillat, M., Sequeira Lopez, M. L. S. (2009). CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am. J. Physiol. Heart Circ. Physiol. 296: H1255-H1262 [Abstract] [Full Text]  
• Jergil, M., Kultima, K., Gustafson, A.-L., Dencker, L., Stigson, M. (2009). Valproic Acid-Induced Deregulation In Vitro of Genes Associated In Vivo with Neural Tube Defects. Toxicol Sci 108: 132-148 [Abstract] [Full Text]  
• Falvo, J. V., Lin, C. H., Tsytsykova, A. V., Hwang, P. K., Thanos, D., Goldfeld, A. E., Maniatis, T. (2008). A dimer-specific function of the transcription factor NFATp. Proc. Natl. Acad. Sci. USA 105: 19637-19642 [Abstract] [Full Text]  
• Wei, J. Q., Shehadeh, L. A., Mitrani, J. M., Pessanha, M., Slepak, T. I., Webster, K. A., Bishopric, N. H. (2008). Quantitative Control of Adaptive Cardiac Hypertrophy by Acetyltransferase p300. Circulation 118: 934-946 [Abstract] [Full Text]  
• Filiano, A. J., Bailey, C. D. C., Tucholski, J., Gundemir, S., Johnson, G. V. W. (2008). Transglutaminase 2 protects against ischemic insult, interacts with HIF1{beta}, and attenuates HIF1 signaling. FASEB J. 22: 2662-2675 [Abstract] [Full Text]  
• Barrett, R. M., Wood, M. A. (2008). Beyond transcription factors: The role of chromatin modifying enzymes in regulating transcription required for memory. Learn. Mem. 15: 460-467 [Abstract] [Full Text]  
• Oliveira, A. M.M., Wood, M. A., McDonough, C. B., Abel, T. (2007). Transgenic mice expressing an inhibitory truncated form of p300 exhibit long-term memory deficits. Learn. Mem. 14: 564-572 [Abstract] [Full Text]  
• Bartholdi, D., Roelfsema, J. H, Papadia, F., Breuning, M. H, Niedrist, D., Hennekam, R. C, Schinzel, A., Peters, D. J M (2007). Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J. Med. Genet. 44: 327-333 [Abstract] [Full Text]  
• Sammons, M., Wan, S. S., Vogel, N. L., Mientjes, E. J., Grosveld, G., Ashburner, B. P. (2006). Negative Regulation of the RelA/p65 Transactivation Function by the Product of the DEK Proto-oncogene. J. Biol. Chem. 281: 26802-26812 [Abstract] [Full Text]  
• Xu, W., Fukuyama, T., Ney, P. A., Wang, D., Rehg, J., Boyd, K., van Deursen, J. M. A., Brindle, P. K. (2006). Global transcriptional coactivators CREB-binding protein and p300 are highly essential collectively but not individually in peripheral B cells. Blood 107: 4407-4416 [Abstract] [Full Text]  

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kasper, L. H. Articles by Brindle, P. K. Search for Related Content PubMed PubMed Citation Articles by Kasper, L. H. Articles by Brindle, P. K.