This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hug, B. A.
Right arrow Articles by Ley, T. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hug, B. A.
Right arrow Articles by Ley, T. J.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Jun 1996, 2906-2912, Vol 16, No. 6
Copyright © 1996, American Society for Microbiology

Analysis of mice containing a targeted deletion of beta-globin locus control region 5' hypersensitive site 3

BA Hug, RL Wesselschmidt, S Fiering, MA Bender, E Epner, M Groudine and TJ Ley
Department of Internal Medicine, Washington University Medical School, St. Louis, Missouri 63110, USA.

To examine the function of murine beta-globin locus region (LCR) 5' hypersensitive site 3 (HS3) in its native chromosomal context, we deleted this site from the mouse germ line by using homologous recombination techniques. Previous experiments with human 5' HS3 in transgenic models suggested that this site independently contains at least 50% of total LCR activity and that it interacts preferentially with the human gamma-globin genes in embryonic erythroid cells. However, in this study, we demonstrate that deletion of murine 5' HS3 reduces expression of the linked embryonic epsilon y- and beta H 1- globin genes only minimally in yolk sac-derived erythroid cells and reduces output of the linked adult beta (beta major plus beta minor) globin genes by approximately 30% in adult erythrocytes. When the selectable marker PGK-neo cassette was left within the HS3 region of the LCR, a much more severe phenotype was observed at all developmental stages, suggesting that PGK-neo interferes with LCR activity when it is retained within the LCR. Collectively, these results suggest that murine 5' HS3 is not required for globin gene switching; importantly, however, it is required for approximately 30% of the total LCR activity associated with adult beta-globin gene expression in adult erythrocytes.


This article has been cited by other articles:

  • Hubert, F.-X., Kinkel, S. A., Crewther, P. E., Cannon, P. Z. F., Webster, K. E., Link, M., Uibo, R., O'Bryan, M. K., Meager, A., Forehan, S. P., Smyth, G. K., Mittaz, L., Antonarakis, S. E., Peterson, P., Heath, W. R., Scott, H. S. (2009). Aire-Deficient C57BL/6 Mice Mimicking the Common Human 13-Base Pair Deletion Mutation Present with Only a Mild Autoimmune Phenotype. J. Immunol. 182: 3902-3918 [Abstract] [Full Text]  
  • Sugamori, K. S., Brenneman, D., Wong, S., Gaedigk, A., Yu, V., Abramovici, H., Rozmahel, R., Grant, D. M. (2007). Effect of Arylamine Acetyltransferase Nat3 Gene Knockout on N-Acetylation in the Mouse. Drug Metab. Dispos. 35: 1064-1070 [Abstract] [Full Text]  
  • Gupta, S., Zhu, H., Zon, L. I., Evans, T. (2006). BMP signaling restricts hemato-vascular development from lateral mesoderm during somitogenesis. Development 133: 2177-2187 [Abstract] [Full Text]  
  • Hu, X., Bulger, M., Bender, M. A., Fields, J., Groudine, M., Fiering, S. (2006). Deletion of the core region of 5' HS2 of the mouse {beta}-globin locus control region reveals a distinct effect in comparison with human {beta}-globin transgenes. Blood 107: 821-826 [Abstract] [Full Text]  
  • Fang, X., Sun, J., Xiang, P., Yu, M., Navas, P. A., Peterson, K. R., Stamatoyannopoulos, G., Li, Q. (2005). Synergistic and Additive Properties of the Beta-Globin Locus Control Region (LCR) Revealed by 5'HS3 Deletion Mutations: Implication for LCR Chromatin Architecture. Mol. Cell. Biol. 25: 7033-7041 [Abstract] [Full Text]  
  • Goetze, S., Baer, A., Winkelmann, S., Nehlsen, K., Seibler, J., Maass, K., Bode, J. (2005). Performance of Genomic Bordering Elements at Predefined Genomic Loci. Mol. Cell. Biol. 25: 2260-2272 [Abstract] [Full Text]  
  • Revell, P. A., Grossman, W. J., Thomas, D. A., Cao, X., Behl, R., Ratner, J. A., Lu, Z. H., Ley, T. J. (2005). Granzyme B and the Downstream Granzymes C and/or F Are Important for Cytotoxic Lymphocyte Functions. J. Immunol. 174: 2124-2131 [Abstract] [Full Text]  
  • Persky, M. E., Murphy, K. M., Farrar, J. D. (2005). IL-12, but Not IFN-{alpha}, Promotes STAT4 Activation and Th1 Development in Murine CD4+ T Cells Expressing a Chimeric Murine/Human Stat2 Gene. J. Immunol. 174: 294-301 [Abstract] [Full Text]  
  • Vieira, K. F., Levings, P. P., Hill, M. A., Crusselle, V. J., Kang, S.-H. L., Engel, J. D., Bungert, J. (2004). Recruitment of Transcription Complexes to the {beta}-Globin Gene Locus in Vivo and in Vitro. J. Biol. Chem. 279: 50350-50357 [Abstract] [Full Text]  
  • Drissen, R., Palstra, R.-J., Gillemans, N., Splinter, E., Grosveld, F., Philipsen, S., de Laat, W. (2004). The active spatial organization of the {beta}-globin locus requires the transcription factor EKLF. Genes Dev. 18: 2485-2490 [Abstract] [Full Text]  
  • Patrinos, G. P., de Krom, M., de Boer, E., Langeveld, A., Imam, A.M. A., Strouboulis, J., de Laat, W., Grosveld, F. G. (2004). Multiple interactions between regulatory regions are required to stabilize an active chromatin hub. Genes Dev. 18: 1495-1509 [Abstract] [Full Text]  
  • Loyd, M. R., Okamoto, Y., Randall, M. S., Ney, P. A. (2003). Role of AP1/NFE2 binding sites in endogenous {alpha}-globin gene transcription. Blood 102: 4223-4228 [Abstract] [Full Text]  
  • Huby, T., Afzal, V., Doucet, C., Lawn, R. M., Gong, E. L., Chapman, M. J., Thillet, J., Rubin, E. M. (2003). Regulation of the Expression of the Apolipoprotein(a) Gene: Evidence for a Regulatory Role of the 5' Distal Apolipoprotein(a) Transcription Control Region Enhancer in Yeast Artificial Chromosome Transgenic Mice. Arterioscler. Thromb. Vasc. Bio. 23: 1633-1639 [Abstract] [Full Text]  
  • Westervelt, P., Lane, A. A., Pollock, J. L., Oldfather, K., Holt, M. S., Zimonjic, D. B., Popescu, N. C., DiPersio, J. F., Ley, T. J. (2003). High-penetrance mouse model of acute promyelocytic leukemia with very low levels of PML-RAR{alpha} expression. Blood 102: 1857-1865 [Abstract] [Full Text]  
  • Marsden, M. D., Fournier, R. E. K. (2003). Chromosomal Elements Regulate Gene Activity and Chromatin Structure of the Human Serpin Gene Cluster at 14q32.1. Mol. Cell. Biol. 23: 3516-3526 [Abstract] [Full Text]  
  • Jackson, D. A., McDowell, J. C., Dean, A. (2003). {beta}-Globin locus control region HS2 and HS3 interact structurally and functionally. Nucleic Acids Res 31: 1180-1190 [Abstract] [Full Text]  
  • Hu, X., Bulger, M., Roach, J. N., Eszterhas, S. K., Olivier, E., Bouhassira, E. E., Groudine, M. T., Fiering, S. (2003). Promoters of the murine embryonic beta -like globin genes Ey and beta h1 do not compete for interaction with the beta -globin locus control region. Proc. Natl. Acad. Sci. USA 100: 1111-1115 [Abstract] [Full Text]  
  • van der Weyden, L., Adams, D. J., Bradley, A. (2002). Tools for targeted manipulation of the mouse genome. Physiol. Genomics 11: 133-164 [Abstract] [Full Text]  
  • Grenda, D. S., Johnson, S. E., Mayer, J. R., McLemore, M. L., Benson, K. F., Horwitz, M., Link, D. C. (2002). Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis. Blood 100: 3221-3228 [Abstract] [Full Text]  
  • Navas, P. A., Li, Q., Peterson, K. R., Swank, R. A., Rohde, A., Roy, J., Stamatoyannopoulos, G. (2002). Activation of the {beta}-like globin genes in transgenic mice is dependent on the presence of the {beta}-locus control region. Hum Mol Genet 11: 893-903 [Abstract] [Full Text]  
  • Chen, Z., Fitzgerald, R. L, Schonfeld, G. (2002). Hypobetalipoproteinemic Mice with a Targeted Apolipoprotein (Apo) B-27.6-specifying Mutation. IN VIVO EVIDENCE FOR AN IMPORTANT ROLE OF AMINO ACIDS 1254-1744 OF ApoB IN LIPID TRANSPORT AND METABOLISM OF THE ApoB-CONTAINING LIPOPROTEIN. J. Biol. Chem. 277: 14135-14145 [Abstract] [Full Text]  
  • Eszterhas, S. K., Bouhassira, E. E., Martin, D. I. K., Fiering, S. (2002). Transcriptional Interference by Independently Regulated Genes Occurs in Any Relative Arrangement of the Genes and Is Influenced by Chromosomal Integration Position. Mol. Cell. Biol. 22: 469-479 [Abstract] [Full Text]  
  • Bender, M. A., Roach, J. N., Halow, J., Close, J., Alami, R., Bouhassira, E. E., Groudine, M., Fiering, S. N. (2001). Targeted deletion of 5'HS1 and 5'HS4 of the {beta}-globin locus control region reveals additive activity of the DNaseI hypersensitive sites. Blood 98: 2022-2027 [Abstract] [Full Text]  
  • Kaufman, R. M., Lu, Z. H., Behl, R., Holt, J. M., Ackers, G. K., Ley, T. J. (2001). Lack of neighborhood effects from a transcriptionally active phosphoglycerate kinase-neo cassette located between the murine {beta}-major and {beta}-minor globin genes. Blood 98: 65-73 [Abstract] [Full Text]  
  • Molete, J. M., Petrykowska, H., Bouhassira, E. E., Feng, Y.-Q., Miller, W., Hardison, R. C. (2001). Sequences Flanking Hypersensitive Sites of the {beta}-Globin Locus Control Region Are Required for Synergistic Enhancement. Mol. Cell. Biol. 21: 2969-2980 [Abstract] [Full Text]  
  • Leach, K. M., Nightingale, K., Igarashi, K., Levings, P. P., Engel, J. D., Becker, P. B., Bungert, J. (2001). Reconstitution of Human {beta}-Globin Locus Control Region Hypersensitive Sites in the Absence of Chromatin Assembly. Mol. Cell. Biol. 21: 2629-2640 [Abstract] [Full Text]  
  • Farrell, C. M., Grinberg, A., Huang, S. P., Chen, D., Pichel, J. G., Westphal, H., Felsenfeld, G. (2000). A large upstream region is not necessary for gene expression or hypersensitive site formation at the mouse beta -globin locus. Proc. Natl. Acad. Sci. USA 97: 14554-14559 [Abstract] [Full Text]  
  • Kildsgaard, J., Hollmann, T. J., Matthews, K. W., Bian, K., Murad, F., Wetsel, R. A. (2000). Cutting Edge: Targeted Disruption of the C3a Receptor Gene Demonstrates a Novel Protective Anti-Inflammatory Role for C3a in Endotoxin-Shock. J. Immunol. 165: 5406-5409 [Abstract] [Full Text]  
  • Bender, M. A., Mehaffey, M. G., Telling, A., Hug, B., Ley, T. J., Groudine, M., Fiering, S. (2000). Independent formation of DnaseI hypersensitive sites in the murine beta -globin locus control region. Blood 95: 3600-3604 [Abstract] [Full Text]  
  • Bauchwitz, R., Costantini, F. (2000). Developmentally distinct effects on human {varepsilon}-, {gamma}- and {delta}-globin levels caused by the absence or altered position of the human {beta}-globin gene in YAC transgenic mice. Hum Mol Genet 9: 561-574 [Abstract] [Full Text]  
  • MacIvor, D. M., Shapiro, S. D., Pham, C. T.N., Belaaouaj, A., Abraham, S. N., Ley, T. J. (1999). Normal Neutrophil Function in Cathepsin G-Deficient Mice. Blood 94: 4282-4293 [Abstract] [Full Text]  
  • Ramakrishnan, V., Reeves, P. S., DeGuzman, F., Deshpande, U., Ministri-Madrid, K., DuBridge, R. B., Phillips, D. R. (1999). Increased thrombin responsiveness in platelets from mice lacking glycoprotein V. Proc. Natl. Acad. Sci. USA 96: 13336-13341 [Abstract] [Full Text]  
  • Kaufman, R. M., Pham, C. T.N., Ley, T. J. (1999). Transgenic Analysis of a 100-kb Human beta -Globin Cluster-Containing DNA Fragment Propagated as a Bacterial Artificial Chromosome. Blood 94: 3178-3184 [Abstract] [Full Text]  
  • Bulger, M., Groudine, M. (1999). Looping versus linking: toward a model for long-distance gene activation. Genes Dev. 13: 2465-2477 [Full Text]  
  • Pham, C. T. N., Ley, T. J. (1999). Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc. Natl. Acad. Sci. USA 96: 8627-8632 [Abstract] [Full Text]  
  • Feng, Y.-Q., Alami, R., Bouhassira, E. E. (1999). Enhancer-Dependent Transcriptional Oscillations in Mouse Erythroleukemia Cells. Mol. Cell. Biol. 19: 4907-4917 [Abstract] [Full Text]  
  • Sargent, T. G., DuBois, C. C., Buller, A. M., Lloyd, J. A. (1999). The Roles of 5'-HS2, 5'-HS3, and the gamma -Globin TATA, CACCC, and Stage Selector Elements in Suppression of beta -Globin Expression in Early Development. J. Biol. Chem. 274: 11229-11236 [Abstract] [Full Text]  
  • Westervelt, P., Ley, T. J. (1999). Seed Versus Soil: The Importance of the Target Cell for Transgenic Models of Human Leukemias. Blood 93: 2143-2148 [Full Text]  
  • Seidl, K. J., Manis, J. P., Bottaro, A., Zhang, J., Davidson, L., Kisselgof, A., Oettgen, H., Alt, F. W. (1999). Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus. Proc. Natl. Acad. Sci. USA 96: 3000-3005 [Abstract] [Full Text]  
  • Saleque, S., Singh, M., Birshtein, B. K. (1999). Ig Heavy Chain Expression and Class Switching In Vitro from an Allele Lacking the 3' Enhancers DNase I-Hypersensitive hs3A and hs1,2. J. Immunol. 162: 2791-2803 [Abstract] [Full Text]  
  • Qiu, G., Harriman, G. R., Stavnezer, J. (1999). I{alpha} exon-replacement mice synthesize a spliced HPRT–C{alpha} transcript which may explain their ability to switch to IgA. Inhibition of switching to IgG in these mice. Int Immunol 11: 37-46 [Abstract] [Full Text]  
  • Trimborn, T., Gribnau, J., Grosveld, F., Fraser, P. (1999). Mechanisms of developmental control of transcription in the murine alpha - and beta -globin loci. Genes Dev. 13: 112-124 [Abstract] [Full Text]  
  • Bender, M.A., Reik, A., Close, J., Telling, A., Epner, E., Fiering, S., Hardison, R., Groudine, M. (1998). Description and Targeted Deletion of 5' Hypersensitive Site 5 and 6 of the Mouse beta -Globin Locus Control Region. Blood 92: 4394-4403 [Abstract] [Full Text]  
  • Sabatino, D. E., Cline, A. P., Gallagher, P. G., Garrett, L. J., Stamatoyannopoulos, G., Forget, B. G., Bodine, D. M. (1998). Substitution of the Human beta -Spectrin Promoter for the Human Agamma -Globin Promoter Prevents Silencing of a Linked Human beta -Globin Gene in Transgenic Mice. Mol. Cell. Biol. 18: 6634-6640 [Abstract] [Full Text]  
  • Manis, J. P., van der Stoep, N., Tian, M., Ferrini, R., Davidson, L., Bottaro, A., Alt, F. W. (1998). Class Switching in B Cells Lacking 3' Immunoglobulin Heavy Chain Enhancers. JEM 188: 1421-1431 [Abstract] [Full Text]  
  • Reik, A., Telling, A., Zitnik, G., Cimbora, D., Epner, E., Groudine, M. (1998). The Locus Control Region Is Necessary for Gene Expression in the Human beta -Globin Locus but Not the Maintenance of an Open Chromatin Structure in Erythroid Cells. Mol. Cell. Biol. 18: 5992-6000 [Abstract] [Full Text]  
  • Gillemans, N., Tewari, R., Lindeboom, F., Rottier, R., de Wit, T., Wijgerde, M., Grosveld, F., Philipsen, S. (1998). Altered DNA-binding specificity mutants of EKLF and Sp1 show that EKLF is an activator of the beta -globin locus control region in vivo. Genes Dev. 12: 2863-2873 [Abstract] [Full Text]  
  • Nielsen, L. B., Kahn, D., Duell, T., Weier, H.-U. G., Taylor, S., Young, S. G. (1998). Apolipoprotein B Gene Expression in a Series of Human Apolipoprotein B Transgenic Mice Generated with recA-assisted Restriction Endonuclease Cleavage-modified Bacterial Artificial Chromosomes. AN INTESTINE-SPECIFIC ENHANCER ELEMENT IS LOCATED BETWEEN 54 AND 62 KILOBASES 5' TO THE STRUCTURAL GENE. J. Biol. Chem. 273: 21800-21807 [Abstract] [Full Text]  
  • Navas, P. A., Peterson, K. R., Li, Q., Skarpidi, E., Rohde, A., Shaw, S. E., Clegg, C. H., Asano, H., Stamatoyannopoulos, G. (1998). Developmental Specificity of the Interaction between the Locus Control Region and Embryonic or Fetal Globin Genes in Transgenic Mice with an HS3 Core Deletion. Mol. Cell. Biol. 18: 4188-4196 [Abstract] [Full Text]  
  • Amrolia, P. J., Gabbard, W., Cunningham, J. M., Jane, S. M. (1998). Maximal Activity of an Erythroid-specific Enhancer Requires the Presence of Specific Protein Binding Sites in Linked Promoters. J. Biol. Chem. 273: 13593-13598 [Abstract] [Full Text]  
  • Martin, F., van Deursen, J. M., Shivdasani, R. A., Jackson, C. W., Troutman, A. G., Ney, P. A. (1998). Erythroid Maturation and Globin Gene Expression in Mice With Combined Deficiency of NF-E2 and Nrf-2. Blood 91: 3459-3466 [Abstract] [Full Text]  
  • Lee, J.-S., Lee, C.-H., Chung, J. H. (1998). Studying the recruitment of Sp1 to the beta -globin promoter with an in vivo method: Protein position identification with nuclease tail (PIN*POINT). Proc. Natl. Acad. Sci. USA 95: 969-974 [Abstract] [Full Text]  
  • Nielsen, L. B., McCormick, S. P. A., Pierotti, V., Tam, C., Gunn, M. D., Shizuya, H., Young, S. G. (1997). Human Apolipoprotein B Transgenic Mice Generated with 207- and 145-Kilobase Pair Bacterial Artificial Chromosomes. EVIDENCE THAT A DISTANT 5'-ELEMENT CONFERS APPROPRIATE TRANSGENE EXPRESSION IN THE INTESTINE. J. Biol. Chem. 272: 29752-29758 [Abstract] [Full Text]  
  • Amrolia, P. J., Ramamurthy, L., Saluja, D., Tanese, N., Jane, S. M., Cunningham, J. M. (1997). The activation domain of the enhancer binding protein p45NF-E2 interacts with TAFII130 and mediates long-range activation of the alpha - and beta -globin gene loci in an erythroid cell line. Proc. Natl. Acad. Sci. USA 94: 10051-10056 [Abstract] [Full Text]  
  • Leder, A., Daugherty, C., Whitney, B., Leder, P. (1997). Mouse zeta - and alpha -Globin Genes: Embryonic Survival, alpha -Thalassemia, and Genetic Background Effects. Blood 90: 1275-1282 [Abstract] [Full Text]  
  • McDevitt, M. A., Shivdasani, R. A., Fujiwara, Y., Yang, H., Orkin, S. H. (1997). A "knockdown" mutation created by cis-element gene targeting reveals the dependence of erythroid cell maturation on the level of transcription factor GATA-1. Proc. Natl. Acad. Sci. USA 94: 6781-6785 [Abstract] [Full Text]  
  • Bresnick, E. H., Tze, L. (1997). Synergism between hypersensitive sites confers long-range gene activation by the beta -globin locus control region. Proc. Natl. Acad. Sci. USA 94: 4566-4571 [Abstract] [Full Text]  
  • Lam, L. T., Bresnick, E. H. (1996). A Novel DNA-binding Protein, HS2NF5, Interacts with a Functionally Important Sequence of the Human beta -Globin Locus Control Region. J. Biol. Chem. 271: 32421-32429 [Abstract] [Full Text]  
  • Magis, W., Fiering, S., Groudine, M., Martin, D. I. K. (1996). An upstream activator of transcription coordinately increases the level and epigenetic stability of gene expression. Proc. Natl. Acad. Sci. USA 93: 13914-13918 [Abstract] [Full Text]  
  • Pham, C. T. N., MacIvor, D. M., Hug, B. A., Heusel, J. W., Ley, T. J. (1996). Long-range disruption of gene expression by a selectable marker cassette. Proc. Natl. Acad. Sci. USA 93: 13090-13095 [Abstract] [Full Text]  
  • Tewari, R, Gillemans, N, Harper, A, Wijgerde, M, Zafarana, G, Drabek, D, Grosveld, F, Philipsen, S (1996). The human beta-globin locus control region confers an early embryonic erythroid-specific expression pattern to a basic promoter driving the bacterial lacZ gene. Development 122: 3991-3999 [Abstract]  
  • Chen, Z., Fitzgerald, R. L., Averna, M. R., Schonfeld, G. (2000). A Targeted Apolipoprotein B-38.9-producing Mutation Causes Fatty Livers in Mice Due to the Reduced Ability of Apolipoprotein B-38.9 to Transport Triglycerides. J. Biol. Chem. 275: 32807-32815 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»