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Molecular and Cellular Biology, April 2002, p. 1961-1970, Vol. 22, No. 7
0270-7306/02/$04.00+0 DOI: 10.1128/MCB.22.7.1961-1970.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Department of Molecular Cell Biology, MGC Center for Biomedical Genetics, Leiden University Medical Center, 2300 RA Leiden, The Netherlands
Received 23 August 2001/ Returned for modification 27 September 2001/ Accepted 14 December 2001
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ABSTRACT |
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INTRODUCTION |
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The acetyltransferases CREB binding protein (CBP) and the related protein p300 function as coactivators for a multitude of transcription factors (9, 23, 58, 63), including CREB (5, 16, 38). This coactivator function is not only due to their intrinsic HAT activity but is also the result of their ability to interact with other HAT proteins such as pCAF and SRC1 family members. Furthermore, CBP and p300 can stabilize the transcription complex by binding to several proteins simultaneously, thereby functioning as a scaffold or physical bridge. While CBP and p300 are essential coactivators for many different transcription factors, the relative importance of these different coactivator functions varies between transcription factors (34, 35, 37). Several lines of evidence underscore the importance of the CBP and p300 proteins in differentiation, growth control, and homeostasis. Firstly, CBP and p300 are required for embryonic development and viability, as observed in knockout mice (66). Secondly, recurrent chromosomal translocations involving CBP and p300 are found in human leukemias (30), and genetic alterations resulting in amino acid changes or protein truncations of p300 are found in solid tumors and tumor cell lines (21, 48). Finally, haploinsufficiency of CBP results in Rubinstein-Taybi syndrome (RTS) in humans, a developmental syndrome characterized by facial abnormalities, broad thumbs, big, broad toes, and mental retardation (54).
Comparison of the amino acid sequences of CBP and p300 from different species revealed the presence of numerous regions of near-identity, including the bromodomain, three cysteine-histidine-rich regions (CH1, -2, and -3), and the HAT domain, while other regions are poorly conserved (4) (see Fig. 1A). The bromodomain, which is found in many chromatin-associated proteins (31, 64), is thought to function as a histone binding motif (17, 29). While the CH1 and CH3 regions serve as binding sites for many different transcription factors and other proteins, the function of the CH2 region, which is partly located within the HAT domain, remains to be determined. Based on sequence homology, part of the CH2 region can be classified as a plant homeodomain (PHD) type zinc finger (1). This type of zinc finger, also named leukemia-associated-protein (LAP) finger (55) or trithorax consensus (TTC) finger (33), is characterized by a C4HC3 motif and is found predominantly in proteins that function at the chromatin level (1). Recently, the solution structures of the PHD fingers of the transcriptional repressor KAP-1 (13) and the Williams's syndrome transcription factor WSTF (52) were determined. In both proteins, two zinc atoms are coordinated by the cysteine and histidine residues in a cross-brace fashion, reminiscent of the zinc coordination found in the RING finger (10) (see Fig. 1B). Furthermore, a number of hydrophobic residues were shown to be involved in the stabilization of this structure. Although more than 300 (mainly nuclear) proteins contain one or more PHD fingers, relatively little is known about the function of this domain. Since many PHD finger-containing proteins reside in large multiprotein complexes, these zinc fingers have been proposed to be involved in protein-protein interactions (1).
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MATERIALS AND METHODS |
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Protein purifications.
Drosophila core histones were purified from embryo nuclear extracts essentially as described by Bulger and Kadonaga (12). Human His-tagged TFIIE34 was expressed in Escherichia coli (DE3), purified with nickel-nitrilotriacetic acid agarose resin (Qiagen), and further purified by SP Sepharose column chromatography as described elsewhere (67). The GST fusion protein of PCAF HAT was expressed in E. coli DH5
and purified according to standard procedures (6). The GST vectors containing wild-type and mutant CBP HAT were transformed into E. coli BL21-CodonPlus(DE3)-RIL (Stratagene). Bacteria were grown in Luria broth in the presence of 50 µM ZnCl2 at 25°C to an optical density at 600 nm of 0.5 and were induced with isopropyl-ß-D-thiogalactopyranoside (0.15 mM) for 2 h at 25°C. Subsequently, bacteria were collected by centrifugation and resuspended in lysis buffer (25 mM HEPES [pH 7.6], 10% glycerol, 500 mM NaCl, 0.01% NP-40, 5 mM dithiothreitol, 2.5 mM MgCl2, 50 µM ZnCl2, and protease inhibitors). Lysozyme was added to a final concentration of 0.15 mg/ml, and the mixture was incubated for 30 min at 4°C with rotation. Lysates were freeze-thawed once, sonicated, cleared by centrifugation at 16,000 x g for 1 h, and stored at -70°C. GST proteins were purified on glutathione beads according to standard procedures (6).
Transient transfection experiments. The human osteosarcoma cell line U-2 OS and the adenovirus type 5-transformed human embryo retina cell line 911 (18) and its derivatives were routinely maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (Gibco Life Technologies), 100 µg of penicillin/ml, and 100 µg of streptomycin/ml. For luciferase reporter assays, cells were plated into 24-well microtiter plates and transfected by using the calcium phosphate coprecipitation method with Gal4 DBD expression plasmids at 200 ng/well, 150 ng of pcDNA-LacZ plasmid (Invitrogen) as an internal control, and 1 µg of a reporter plasmid [or pBluescript SK(-) in the case of the 911 reporter cells]. Transfections with CREB in 911 reporter cells contained 100 ng of Gal4 DBD-CREB, 100 ng of PKA expression vector, 100 ng of pcDNA-CBP, and 1 µg of pBluescript SK(-). After 24 h, cells were washed with 1x HEPES-buffered saline and then maintained in medium for another 24 h. Cells were then washed with phosphate-buffered saline (PBS) and harvested in lysis buffer (25 mM Tris phosphate [pH 7.8], 2 mM dithiothreitol, 2 mM 1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid, 10% glycerol, 1% Triton X-100). Extracts were assayed for luciferase activity according to the manufacturer's protocol (Promega) and for ß-galactosidase activity (6) as a control. For immunoprecipitation experiments, cells were plated in 9-cm dishes and transfected with Fugene (Roche) with 10 µg of expression plasmid.
Isolation of reporter cell lines. 911 cells were transfected with the 5xGal-E1BTATA-Luc reporter or the 5xGal-AdMLTATA-Luc reporter together with a CMV-neo plasmid by the calcium phosphate coprecipitation method as described above. After 24 h, cells were replated into 5-cm dishes, and Geneticin (G418; 600 µg/ml) was added. Resistant clones were isolated after 6 days and cultured under continuous G418 selection.
Immunoprecipitations. Cells, which had previously been transfected, were washed in ice-cold PBS, collected in ice-cold lysis buffer (50 mM Tris-HCl [pH 7.5], 250 mM NaCl, 5 mM EDTA, 0.1% NP-40, and protease inhibitors), and incubated for 30 min at 4°C. Lysates were freeze-thawed once and cleared by centrifugation. Protein concentrations were determined by the Bradford method. Cell lysates containing equal amounts of protein (600 µg) were incubated for 3 to 4 h at 4°C under constant rotation with a polyclonal antibody against the Gal4 DBD (SC-570; Santa Cruz) which had been precoupled to protein A-Sepharose beads. Immunocomplexes were washed four times in lysis buffer, and one-sixth of the amount (corresponding to 100 µg of cell lysate) was taken for Western blot analysis, while the remainder was used in acetyltransferase assays.
Acetyltransferase assays. Acetyltransferases expressed in mammalian cells or bacteria were isolated by immunoprecipitation or GST purification, respectively, as described above. In some experiments the acetyltransferases were preincubated with the chelating agent 1,10-phenanthroline (5 or 10 mM; Sigma) for 30 min at 4°C. Acetyltransferases were incubated directly with Drosophila core histones (5 µg) or purified TFIIE34 (2 µg) in AIPH buffer (20 mM Tris-HCl [pH 8.0], 60 mM NaCl, 2 mM EDTA, 0.2% NP-40, 40 µM phenylmethylsulfonyl fluoride) containing [14C]acetyl-CoA (0.05 µCi) for 40 min at 30°C. Reactions were stopped by addition of 2x sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample buffer. Proteins were separated on SDS-PAGE gels with 15% (for histones) or 10% (for TFIIE34) polyacrylamide, fixed, and stained with Coomassie brilliant blue. Subsequently, gels were enhanced with Amplify (Amersham) and dried, and labeled proteins were visualized by fluorography.
Western blotting. Proteins, separated by SDS-PAGE, were transferred onto Immobilon membranes (Millipore). Blots were blocked in TBST (10 mM Tris-HCl [pH 8.0], 150 mM NaCl, 0.05% Tween 20) containing 5% nonfat dried milk powder and subsequently incubated with 1:1,000 dilutions of a monoclonal antibody against the Gal4 DBD (SC-510; Santa Cruz) or a polyclonal antibody against acetylated lysine residues (06-933; Upstate Biotechnology). After a wash, blots were incubated with peroxidase-conjugated antibodies (1:10,000; Jackson ImmunoResearch Laboratories). Blots were washed again, and immunoreactive bands were visualized by enhanced chemiluminescence.
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RESULTS |
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To analyze the in vitro HAT activity of wild-type CBP and the mutants described above, we first overexpressed the region of CBP encompassing the HAT domain (amino acids 1099 to 1758) fused to Gal4 DBD in U-2 OS cells. Subsequently, these proteins were isolated by immunoprecipitation with an anti-Gal4 DBD antibody and tested for the ability to acetylate purified Drosophila core histones in vitro. As observed previously (35, 51), Gal4 DBD-CBP HAT acetylated core histones in vitro, with a preference for histones H3 and H4 (Fig. 2). Mutation of the six most C-terminal zinc-coordinating residues (C1284, C1287, H1292, C1295, C1309, and C1312) and F1307, which is part of the hydrophobic core of PHD proteins (13), resulted in an almost-complete loss of HAT activity. A second class of mutants, including those with mutations of the N-terminal cysteines C1238 and C1241, the conserved hydrophobic F1281, and the nonconserved P1280, V1282, and H1298, displayed reduced activity. The third group of mutants, encompassing the nonconserved residues T1243 and K1285, showed no significant change in HAT activity from that for wild-type CBP. As expected, the known F1541A and L1690K/C1691L HAT mutants showed severely reduced capacities to acetylate histones (34, 46). As a control, Western blot analysis was performed; it showed that comparable amounts of the Gal4 DBD fusions were immunoprecipitated (Fig. 2A). These findings suggest that the CBP HAT domain contains an essential PHD type zinc finger, since mutation of amino acids that are part of the PHD finger signature results in a partial or complete loss of HAT activity.
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Taken together, these results strongly support the notion that the region between amino acids 1238 and 1312 of CBP forms a PHD type (C4HC3) zinc finger which is essential for the ability to acetylate histones in vitro.
The PHD finger of CBP is also essential for the acetylation of nonhistone proteins. Since histones are not the only in vitro substrates of the acetyltransferase activity of CBP, we next examined wild-type CBP and a selection of mutants for their abilities to acetylate nonhistone proteins. For this, the small (TFIIE34) and large (TFIIE56) subunits of the basal transcription factor TFIIE were purified from bacteria and incubated with immunopurified wild-type and mutant Gal4 DBD-CBP HAT proteins. As shown previously (28), wild-type CBP acetylated the small subunit of TFIIE (TFIIE34) but not the larger TFIIE56 subunit (Fig. 4 and data not shown). Acetylation of TFIIE34 by the T1243A mutant was comparable to that by wild-type CBP, whereas the C1287A and F1541A mutants failed to acetylate TFIIE34 and the F1307A and C1241A mutants showed reduced activity. Similar results were obtained with TFIIF (data not shown), another substrate for in vitro acetylation by CBP (28). Furthermore, Western blot analysis of the Gal4 DBD-CBP HAT proteins showed a pattern for CBP autoacetylation, detected with an antibody against acetylated lysine residues, similar to that for TFIIE34 acetylation (Fig. 4). Thus, our mutational analysis of CBP yielded similar results for core histones (Fig. 2 and 3), TFIIE (Fig. 4), CBP itself (Fig. 4), and TFIIF (data not shown). This suggests that the PHD finger plays a general role in the acetylation reaction and is not involved in determining substrate specificity.
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Effect of PHD mutations on full-length CBP. Since regions other than the HAT domain are also important for CBP to function as a transcriptional coactivator (34, 35, 37), we next investigated the importance of the PHD finger for the HAT function and for transcriptional activity in the context of the full-length protein. First, Gal4 DBD fusions of full-length CBP and a selection of mutants were overexpressed in cells, isolated by immunoprecipitation, and tested for their abilities to acetylate core histones. As shown in Fig. 7A, wild-type CBP and the T1243A mutant acetylated histones to similar extents, while the C1287A and F1541A mutants showed dramatic reductions in activity. Mutation of C1241 or F1307 resulted in a partial reduction in activity, most clearly in the former mutant.
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To examine the role of the PHD finger on promoters within a natural chromatin environment, we isolated individual clones of 911 cells with Gal4 reporters stably integrated into the genome. Introduction of the full-length CBP protein and the mutant versions fused to the Gal4 DBD into cells stably transfected with the 5xGal4-AdMLTATA-Luc reporter (clone 10) resulted in a pattern of activation similar to that observed when a transiently transfected reporter was used (Fig. 7B, center panel). Similar results were obtained with several other independent clones (data not shown), indicating that these results are not due to specific integration events. Furthermore, when cells with an integrated 5xGal4-E1BTATA-Luc reporter (clone 8) were used, the transcriptional-activity pattern of wild-type CBP and the mutant versions was again similar (Fig. 7B, bottom panel).
Next we investigated the abilities of PHD mutants to potentiate transcription when they are not tethered directly to a promoter via the Gal4 DBD. For this, cells with an integrated 5xGal4-E1BTATA-Luc reporter (clone 8) were transfected with a Gal4-DBD fusion of CREB, a transcription factor which requires CBP (5, 34), in the absence or presence of CBP and the C1241A and C1287A PHD mutants. Recruitment of CBP by CREB requires PKA-mediated phosphorylation of CREB at serine 133 (5, 16, 38). As shown in Fig. 8, CBP potentiated PKA-activated CREB, while the C1241A and C1287A PHD mutants, particularly the latter, showed reduced activity. No effect of CBP was observed in the absence of PKA or when the PKA phosphorylation site in CREB was mutated to alanine (S133A), indicating that the stimulatory effect of CBP depends strictly on its recruitment by activated CREB.
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DISCUSSION |
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Interestingly, several lines of evidence strongly link amino acid substitutions in PHD fingers to human disease. First, mutations in the PHD finger of the ATRX protein, resulting in conversion of the first and sixth zinc-coordinating cysteines into arginine and phenylalanine, respectively, predispose individuals to -thalassemia (22). Second, two point mutations in the PHD finger of the AIRE-1 gene, which is linked to autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), have been described; one of these alters the third cysteine into a tyrosine residue (8, 56). Third, a number of point mutations have been found in the ING1 gene, a candidate tumor suppressor gene, one of which changes the second cysteine of the PHD finger into a serine residue (24). A single amino acid change (R1379P) in CBP, resulting in complete loss of HAT activity, was recently identified in a patient suffering from RTS (49). Based on our results demonstrating that single amino acid changes in the PHD finger of CBP result in partial or complete losses of HAT activity, it will be of interest to examine whether such mutations are present in RTS patients.
The presence of a bona fide PHD finger is unique to the HAT domain of the CBP/p300 subfamily. When PHD fingers were first identified, they were suggested to be involved in protein-protein interactions (1). Indeed, PHD fingers have been shown to be essential for the interactions of KAP-1 with Mi-2 (57), ZMOX1a with 14-3-3 proteins (25), and SPBP with RNF4 (41). Furthermore, a special type of zinc finger, the extended PHD finger, was shown to be responsible for oligomerization of the AF10 protein (40). Given the location of the PHD finger within the HAT domain, it is possible that in CBP this zinc finger is involved in substrate binding, as shown for the unrelated C2HC zinc finger in the MYST family member MOF (3). The fact that the PHD mutations affected the acetylation of all substrates tested to similar extents implies that in CBP the PHD finger would function as a relatively aspecific docking site for acetylation substrates. This might explain the promiscuous enzymatic behavior of CBP/p300 compared to that of several other HATs (60). Furthermore, such a low-specificity binding function of the PHD finger could also contribute to the interaction of CBP/p300 with chromatin, since the bromodomain of p300 was recently shown to be essential but not sufficient for this interaction (43). Alternatively, the PHD finger might not function primarily in intermolecular protein interactions but mainly serve in maintaining the structural integrity of the CBP/p300 HAT domain. In either case, however, it is clear that the PHD finger cannot be functionally separated from the HAT domain and should therefore be viewed as an integral part of the enzymatic core of the CBP protein.
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ACKNOWLEDGMENTS |
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E.K. and H.T were supported by the Dutch Cancer Society (KWF).
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FOOTNOTES |
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REFERENCES |
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2. Ait-Si-Ali, S., S. Ramirez, F. X. Barre, F. Dkhissi, L. Magnaghi-Jaulin, J. A. Girault, P. Robin, M. Knibiehler, L. L. Pritchard, B. Ducommun, D. Trouche, and A. Harel-Bellan. 1998. Histone acetyltransferase activity of CBP is controlled by cycle-dependent kinases and oncoprotein E1A. Nature 396:184-186.[CrossRef][Medline]
3. Akhtar, A., and P. B. Becker. 2001. The histone H4 acetyltransferase MOF uses a C2HC zinc finger for substrate recognition. EMBO Rep. 2:113-118.[CrossRef][Medline]
4. Arany, Z., W. R. Sellers, D. M. Livingston, and R. Eckner. 1994. E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators. Cell 77:799-800.[CrossRef][Medline]
5. Arias, J., A. S. Alberts, P. Brindle, F. X. Claret, T. Smeal, M. Karin, J. Feramisco, and M. Montminy. 1994. Activation of cAMP and mitogen responsive genes relies on a common nuclear factor. Nature 370:226-229.[CrossRef][Medline]
6. Ausubel, F. M., R. Brent, R. Kingston, D. Moore, J. J. Seidman, J. Smith, and K. Struhl. 1993. Current protocols in molecular biology. John Wiley & Sons, New York, N.Y.
7. Bannister, A. J., and T. Kouzarides. 1996. The CBP co-activator is a histone acetyltransferase. Nature 384:641-643.[CrossRef][Medline]
8. Bjorses, P., M. Halonen, J. J. Palvimo, M. Kolmer, J. Aaltonen, P. Ellonen, J. Perheentupa, I. Ulmanen, and L. Peltonen. 2000. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am. J. Hum. Genet. 66:378-392.[CrossRef][Medline]
9.
Blobel, G. A. 2000. CREB-binding protein and p300: molecular integrators of hematopoietic transcription. Blood 95:745-755.
10. Borden, K. L., and P. S. Freemont. 1996. The RING finger domain: a recent example of a sequence-structure family. Curr. Opin. Struct. Biol. 6:395-401.[CrossRef][Medline]
11.
Bordoli, L., M. Netsch, U. Luthi, W. Lutz, and R. Eckner. 2001. Plant orthologs of p300/CBP: conservation of a core domain in metazoan p300/CBP acetyltransferase-related proteins. Nucleic Acids Res. 29:589-597.
12. Bulger, M., and J. T. Kadonaga. 1994. Biochemical reconstitution of chromatin with physiological nucleosome spacing. Methods Mol. Genet. 5:241-262.
13. Capili, A. D., D. C. Schultz, F. J. Rauscher III, and K. L. Borden. 2001. Solution structure of the PHD domain from the KAP-1 corepressor: structural determinants for PHD, RING and LIM zinc-binding domains. EMBO J. 20:165-177.[CrossRef][Medline]
14.
Chen, C. J., Z. Deng, A. Y. Kim, G. A. Blobel, and P. M. Lieberman. 2001. Stimulation of CREB binding protein nucleosomal histone acetyltransferase activity by a class of transcriptional activators. Mol. Cell. Biol. 21:476-487.
15. Cheung, W. L., S. D. Briggs, and C. D. Allis. 2000. Acetylation and chromosomal functions. Curr. Opin. Cell Biol. 12:326-333.[CrossRef][Medline]
16. Chrivia, J. C., R. P. Kwok, N. Lamb, M. Hagiwara, M. R. Montminy, and R. H. Goodman. 1993. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 365:855-859.[CrossRef][Medline]
17. Dhalluin, C., J. E. Carlson, L. Zeng, C. He, A. K. Aggarwal, and M. M. Zhou. 1999. Structure and ligand of a histone acetyltransferase bromodomain. Nature 399:491-496.[CrossRef][Medline]
18. Fallaux, F. J., O. Kranenburg, S. J. Cramer, A. Houweling, H. Van Ormondt, R. C. Hoeben, and A. J. Van Der Eb. 1996. Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum. Gene Ther. 7:215-222.[Medline]
19. Flint, K. J., and N. C. Jones. 1991. Differential regulation of three members of the ATF/CREB family of DNA-binding proteins. Oncogene 6:2019-2026.[Medline]
20. Fujii, G., R. Tsuchiya, Y. Itoh, K. Tashiro, and S. Hirohashi. 1998. Molecular cloning and expression of Xenopus p300/CBP. Biochim. Biophys. Acta 1443:41-54.[Medline]
21. Gayther, S. A., S. J. Batley, L. Linger, A. Bannister, K. Thorpe, S. F. Chin, Y. Daigo, P. Russell, A. Wilson, H. M. Sowter, J. D. Delhanty, B. A. Ponder, T. Kouzarides, and C. Caldas. 2000. Mutations truncating the EP300 acetylase in human cancers. Nat. Genet. 24:300-303.[CrossRef][Medline]
22. Gibbons, R. J., S. Bachoo, D. J. Picketts, S. Aftimos, B. Asenbauer, J. Bergoffen, S. A. Berry, N. Dahl, A. Fryer, K. Keppler, K. Kurosawa, M. L. Levin, M. Masuno, G. Neri, M. E. Pierpont, S. F. Slaney, and D. R. Higgs. 1997. Mutations in transcriptional regulator ATRX establish the functional significance of a PHD-like domain. Nat. Genet. 17:146-148.[CrossRef][Medline]
23.
Goodman, R. H., and S. Smolik. 2000. CBP/p300 in cell growth, transformation, and development. Genes Dev. 14:1553-1577.
24.
Gunduz, M., M. Ouchida, K. Fukushima, H. Hanafusa, T. Etani, S. Nishioka, K. Nishizaki, and K. Shimizu. 2000. Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas. Cancer Res. 60:3143-3146.
25.
Halbach, T., N. Scheer, and W. Werr. 2000. Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins. Nucleic Acids Res. 28:3542-3550.
26. Hamamori, Y., V. Sartorelli, V. Ogryzko, P. L. Puri, H. Y. Wu, J. Y. Wang, Y. Nakatani, and L. Kedes. 1999. Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A. Cell 96:405-413.[CrossRef][Medline]
27. Henttu, P. M., E. Kalkhoven, and M. G. Parker. 1997. AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen receptor depend on a lysine residue conserved in nuclear receptors. Mol. Cell. Biol. 17:1832-1839.[Abstract]
28. Imhof, A., X. J. Yang, V. V. Ogryzko, Y. Nakatani, A. P. Wolffe, and H. Ge. 1997. Acetylation of general transcription factors by histone acetyltransferases. Curr. Biol. 7:689-692.[CrossRef][Medline]
29.
Jacobson, R. H., A. G. Ladurner, D. S. King, and R. Tjian. 2000. Structure and function of a human TAFII250 double bromodomain module. Science 288:1422-1425.
30. Jacobson, S., and L. Pillus. 1999. Modifying chromatin and concepts of cancer. Curr. Opin. Genet. Dev. 9:175-184.[CrossRef][Medline]
31. Jeanmougin, F., J. M. Wurtz, B. Le Douarin, P. Chambon, and R. Losson. 1997. The bromodomain revisited. Trends Biochem. Sci. 22:151-153.[CrossRef][Medline]
32.
Kingston, R. E., and G. J. Narlikar. 1999. ATP-dependent remodeling and acetylation as regulators of chromatin fluidity. Genes Dev. 13:2339-2352.
33. Koken, M. H., A. Saib, and H. de The. 1995. A C4HC3 zinc finger motif. C. R. Acad. Sci. Ser. III 318:733-739.[Medline]
34.
Korzus, E., J. Torchia, D. W. Rose, L. Xu, R. Kurokawa, E. M. McInerney, T. M. Mullen, C. K. Glass, and M. G. Rosenfeld. 1998. Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science 279:703-707.
35.
Kraus, W. L., E. T. Manning, and J. T. Kadonaga. 1999. Biochemical analysis of distinct activation functions in p300 that enhance transcription initiation with chromatin templates. Mol. Cell. Biol. 19:8123-8135.
36. Kuo, M. H., and C. D. Allis. 1998. Roles of histone acetyltransferases and deacetylases in gene regulation. Bioessays 20:615-626.[CrossRef][Medline]
37.
Kurokawa, R., D. Kalafus, M. H. Ogliastro, C. Kioussi, L. Xu, J. Torchia, M. G. Rosenfeld, and C. K. Glass. 1998. Differential use of CREB binding protein-coactivator complexes. Science 279:700-703.
38. Kwok, R. P., J. R. Lundblad, J. C. Chrivia, J. P. Richards, H. P. Bachinger, R. G. Brennan, S. G. Roberts, M. R. Green, and R. H. Goodman. 1994. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature 370:223-226.[CrossRef][Medline]
39.
Lemon, B., and R. Tjian. 2000. Orchestrated response: a symphony of transcription factors for gene control. Genes Dev. 14:2551-2569.
40. Linder, B., R. Newman, L. K. Jones, S. Debernardi, B. D. Young, P. Freemont, C. P. Verrijzer, and V. Saha. 2000. Biochemical analyses of the AF10 protein: the extended LAP/PHD-finger mediates oligomerisation. J. Mol. Biol. 299:369-378.[CrossRef][Medline]
41.
Lyngso, C., G. Bouteiller, C. K. Damgaard, D. Ryom, S. Sanchez-Munoz, P. L. Norby, B. J. Bonven, and P. Jorgensen. 2000. Interaction between the transcription factor SPBP and the positive cofactor RNF4. An interplay between protein binding zinc fingers. J. Biol. Chem. 275:26144-26149.
42.
Mak, H. Y., S. Hoare, P. M. Henttu, and M. G. Parker. 1999. Molecular determinants of the estrogen receptor-coactivator interface. Mol. Cell. Biol. 19:3895-3903.
43.
Manning, E. T., T. Ikehara, T. Ito, J. T. Kadonaga, and W. L. Kraus. 2001. p300 forms a stable, template-committed complex with chromatin: role for the bromodomain. Mol. Cell. Biol. 21:3876-3887.
44. Marmorstein, R. 2001. Protein modules that manipulate histone tails for chromatin regulation. Nat. Rev. Mol. Cell Biol. 2:422-432.[CrossRef][Medline]
45. Marmorstein, R., and S. Y. Roth. 2001. Histone acetyltransferases: function, structure, and catalysis. Curr. Opin. Genet. Dev. 11:155-161.[CrossRef][Medline]
46. Martinez-Balbas, M. A., A. J. Bannister, K. Martin, P. Haus-Seuffert, M. Meisterernst, and T. Kouzarides. 1998. The acetyltransferase activity of CBP stimulates transcription. EMBO J. 17:2886-2893.[CrossRef][Medline]
47.
Mellon, P. L., C. H. Clegg, L. A. Correll, and G. S. McKnight. 1989. Regulation of transcription by cyclic AMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 86:4887-4891.
48. Muraoka, M., M. Konishi, R. Kikuchi-Yanoshita, K. Tanaka, N. Shitara, J. M. Chong, T. Iwama, and M. Miyaki. 1996. p300 gene alterations in colorectal and gastric carcinomas. Oncogene 12:1565-1569.[Medline]
49.
Murata, T., R. Kurokawa, A. Krones, K. Tatsumi, M. Ishii, T. Taki, M. Masuno, H. Ohashi, M. Yanagisawa, M. G. Rosenfeld, C. K. Glass, and Y. Hayashi. 2001. Defect of histone acetyltransferase activity of the nuclear transcriptional coactivator CBP in Rubinstein-Taybi syndrome. Hum. Mol. Genet. 10:1071-1076.
50. Neuwald, A. F., and D. Landsman. 1997. GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPT10 protein. Trends Biochem. Sci. 22:154-155.[CrossRef][Medline]
51. Ogryzko, V. V., R. L. Schiltz, V. Russanova, B. H. Howard, and Y. Nakatani. 1996. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 87:953-959.[CrossRef][Medline]
52. Pascual, J., M. Martinez-Yamout, H. J. Dyson, and P. E. Wright. 2000. Structure of the PHD zinc finger from human Williams-Beuren syndrome transcription factor. J. Mol. Biol. 304:723-729.[CrossRef][Medline]
53.
Perissi, V., J. S. Dasen, R. Kurokawa, Z. Wang, E. Korzus, D. W. Rose, C. K. Glass, and M. G. Rosenfeld. 1999. Factor-specific modulation of CREB-binding protein acetyltransferase activity. Proc. Natl. Acad. Sci. USA 96:3652-3657.
54. Petrij, F., R. H. Giles, H. G. Dauwerse, J. J. Saris, R. C. Hennekam, M. Masuno, N. Tommerup, G. J. van Ommen, R. H. Goodman, D. J. Peters, et al. 1995. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature 376:348-351.[CrossRef][Medline]
55.
Saha, V., T. Chaplin, A. Gregorini, P. Ayton, and B. D. Young. 1995. The leukemia-associated-protein (LAP) domain, a cysteine-rich motif, is present in a wide range of proteins, including MLL, AF10, and MLLT6 proteins. Proc. Natl. Acad. Sci. USA 92:9737-9741.
56. Saugier-Veber, P., N. Drouot, L. M. Wolf, J. M. Kuhn, T. Frebourg, and H. Lefebvre. 2001. Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Eur. J. Endocrinol. 144:347-351.[Abstract]
57.
Schultz, D. C., J. R. Friedman, and F. J. Rauscher III. 2001. Targeting histone deacetylase complexes via KRAB-zinc finger proteins: the PHD and bromodomains of KAP-1 form a cooperative unit that recruits a novel isoform of the Mi-2 subunit of NuRD. Genes Dev. 15:428-443.
58. Shikama, N., J. Lyon, and N. B. La Thangue. 2000. The p300/CBP family: integrating signals with transcription factors and chromatin. Trends Cell Biol. 7:230-236.[CrossRef]
59. Soutoglou, E., B. Viollet, M. Vaxillaire, M. Yaniv, M. Pontoglio, and I. Talianidis. 2001. Transcription factor-dependent regulation of CBP and P/CAF histone acetyltransferase activity. EMBO J. 20:1984-1992.[CrossRef][Medline]
60.
Sterner, D. E., and S. L. Berger. 2000. Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64:435-459.
61. Tan, S. 2001. One HAT size fits all? Nat. Struct. Biol. 8:8-10.[CrossRef][Medline]
62. Turner, B. M. 2000. Histone acetylation and an epigenetic code. Bioessays 22:836-845.[CrossRef][Medline]
63.
Vo, N., and R. H. Goodman. 2001. CREB-binding protein and p300 in transcriptional regulation. J. Biol. Chem. 276:13505-13508.
64. Winston, F., and C. D. Allis. 1999. The bromodomain: a chromatin-targeting module? Nat. Struct. Biol. 6:601-604.[CrossRef][Medline]
65. Yan, Y., N. A. Barlev, R. H. Haley, S. L. Berger, and R. Marmorstein. 2000. Crystal structure of yeast esa1 suggests a unified mechanism for catalysis and substrate binding by histone acetyltransferases. Mol. Cell 6:1195-1205.[CrossRef][Medline]
66. 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]
67.
Yokomori, K., C. P. Verrijzer, and R. Tjian. 1998. An interplay between TATA box-binding protein and transcription factors IIE and IIA modulates DNA binding and transcription. Proc. Natl. Acad. Sci. USA 95:6722-6727.
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