Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 198, Issue 12, Pages 1937-1949Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030714
Keywords
Brg1; SWI-SNF; chromatin; T cell; development
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Funding
- NICHD NIH HHS [R01 HD036655] Funding Source: Medline
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Mammalian SWI-SNF-related complexes use brahma-related gene 1 (Big1) as a catalytic subunit to remodel nucleosonies 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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