The Role of Brg1, a Catalytic Subunit of Mammalian Chromatin-remodeling Complexes, in T Cell Development

Thomas C. Gebuhr, Grigoriy I. Kovalev, Scott Bultman, Virginia Godfrey, Lishan Su, Terry Magnuson

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

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 depression 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.

Original languageEnglish
Pages (from-to)1937-1949
Number of pages13
JournalJournal of Experimental Medicine
Volume198
Issue number12
DOIs
Publication statusPublished - 15 Dec 2003
Externally publishedYes

Keywords

  • Brg1
  • Chromatin
  • Development
  • SWI-SNF
  • T cell

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