QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gad.1364105v1 19/23/2849    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bultman, S. J. Articles by Magnuson, T. Search for Related Content PubMed PubMed Citation Articles by Bultman, S. J. Articles by Magnuson, T. Social Bookmarking                   What's this?

RESEARCH PAPER

A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in -globin expression and erythroid development

Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA

The Brg1 catalytic subunit of SWI/SNF-related complexes has been implicated in many developmental and physiological processes, but null homozygotes die as blastocysts prior to implantation. To circumvent this early embryonic lethality, we performed an ENU mutagenesis screen and generated a Brg1 hypomorph mutation in the ATPase domain. The mutant Brg1 protein is stable, assembles into SWI/SNF-related complexes, and exhibits normal ATPase activity but is unable to establish DNase I hypersensitivity sites characteristic of open chromatin. Mutant embryos develop normally until midgestation but then exhibit a distinct block in the development of the erythroid lineage, leading to anemia and death. The mutant Brg1 protein is recruited to the -globin locus, but chromatin remodeling and transcription are perturbed. Histone acetylation and DNA methylation are also affected. To our knowledge, Brg1 is the first chromatin-modifying factor shown to be required for -globin regulation and erythropoiesis in vivo. Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling.

[Keywords: ATPase; globin; Brg1; locus-control region; SWI/SNF; chromatin remodeling]

Received August 10, 2005; revised version accepted September 29, 2005.

Supplemental material is available at http://www.genesdev.org.

² Corresponding author.

E-MAIL scott_bultman{at}med.unc.edu; FAX (919) 843-4682.

¹ Present address: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. Sengupta, K. Chen, E. Milot, and J. J. Bieker Acetylation of EKLF Is Essential for Epigenetic Modification and Transcriptional Activation of the {beta}-Globin Locus Mol. Cell. Biol., October 15, 2008; 28(20): 6160 - 6170. [Abstract] [Full Text] [PDF]

				Z. Yan, Z. Wang, L. Sharova, A. A. Sharov, C. Ling, Y. Piao, K. Aiba, R. Matoba, W. Wang, and M. S. H. Ko BAF250B-Associated SWI/SNF Chromatin-Remodeling Complex Is Required to Maintain Undifferentiated Mouse Embryonic Stem Cells Stem Cells, May 1, 2008; 26(5): 1155 - 1165. [Abstract] [Full Text] [PDF]

				K. W. Trotter, H.-Y. Fan, M. L. Ivey, R. E. Kingston, and T. K. Archer The HSA Domain of BRG1 Mediates Critical Interactions Required for Glucocorticoid Receptor-Dependent Transcriptional Activation In Vivo Mol. Cell. Biol., February 15, 2008; 28(4): 1413 - 1426. [Abstract] [Full Text] [PDF]

				C. T. Griffin, J. Brennan, and T. Magnuson The chromatin-remodeling enzyme BRG1 plays an essential role in primitive erythropoiesis and vascular development Development, February 1, 2008; 135(3): 493 - 500. [Abstract] [Full Text] [PDF]

				M. Szyf The Dynamic Epigenome and its Implications in Toxicology Toxicol. Sci., November 1, 2007; 100(1): 7 - 23. [Abstract] [Full Text] [PDF]

				M. Zhang, H. Fang, J. Zhou, and B. P. Herring A Novel Role of Brg1 in the Regulation of SRF/MRTFA-dependent Smooth Muscle-specific Gene Expression J. Biol. Chem., August 31, 2007; 282(35): 25708 - 25716. [Abstract] [Full Text] [PDF]

				J. A. Horsfield, S. H. Anagnostou, J. K.-H. Hu, K. H. Y. Cho, R. Geisler, G. Lieschke, K. E. Crosier, and P. S. Crosier Cohesin-dependent regulation of Runx genes Development, July 15, 2007; 134(14): 2639 - 2649. [Abstract] [Full Text] [PDF]

				S.-I. Kim, S. J. Bultman, H. Jing, G. A. Blobel, and E. H. Bresnick Dissecting Molecular Steps in Chromatin Domain Activation during Hematopoietic Differentiation Mol. Cell. Biol., June 15, 2007; 27(12): 4551 - 4565. [Abstract] [Full Text] [PDF]

				T. Ueda, R. Watanabe-Fukunaga, H. Ogawa, H. Fukuyama, Y. Higashi, S. Nagata, and R. Fukunaga Critical role of the p400/mDomino chromatin-remodeling ATPase in embryonic hematopoiesis Genes Cells, May 1, 2007; 12(5): 581 - 592. [Abstract] [Full Text] [PDF]

				C. S. Kwon, K.-i. Hibara, J. Pfluger, S. Bezhani, H. Metha, M. Aida, M. Tasaka, and D. Wagner A role for chromatin remodeling in regulation of CUC gene expression in the Arabidopsis cotyledon boundary Development, August 15, 2006; 133(16): 3223 - 3230. [Abstract] [Full Text] [PDF]

				S. J. Bultman, T. C. Gebuhr, H. Pan, P. Svoboda, R. M. Schultz, and T. Magnuson Maternal BRG1 regulates zygotic genome activation in the mouse. Genes & Dev., July 1, 2006; 20(13): 1744 - 1754. [Abstract] [Full Text] [PDF]