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Publication : The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development.

First Author  Gebuhr TC Year  2003
Journal  J Exp Med Volume  198
Issue  12 Pages  1937-49
PubMed ID  14676303 Mgi Jnum  J:87219
Mgi Id  MGI:2683887 Doi  10.1084/jem.20030714
Citation  Gebuhr TC, et al. (2003) The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med 198(12):1937-49
abstractText  Mammalian SWI-SNF-related complexes use brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes and regulate transcription. Recent biochemical data has linked Brg1 function to genes important for T lymphocyte differentiation. To investigate the role of SWI-SNF-related complexes in this lineage, we ablated Brg1 function in T lymphocytes. T cell-specific Brg1-deficient mice showed profound thymic abnormalities, CD4 derepression at the double negative (DN; CD4- CD8-) stage, and a developmental block at the DN to double positive (CD4+ CD8+) transition. 5'-bromo-2'-deoxyuridine incorporation and annexin V staining establish a role for Brg1 complexes in the regulation of thymocyte cell proliferation and survival. This Brg1-dependent cell survival is specific for developing thymocytes as indicated by the presence of Brg1-deficient mature T lymphocytes that have escaped the developmental block in the thymus. However, reductions in peripheral T cell populations lead to immunodeficiency and compromised health of mutant mice. These results highlight the importance of chromatin-remodeling complexes at different stages in the development of a mammalian cell lineage.
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