Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development

Tian H. Chi, Mimi Wan, Peggy P. Lee, Koichi Akashi, Daniel Metzger, Pierre Chambon, Christopher B. Wilson, Gerald R. Crabtree

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

T cells develop through distinct stages directed by a series of signals. We explored the roles of SWI/SNF-like BAF chromatin remodeling complexes in this process by progressive deletion of the ATPase subunit, Brg, through successive stages of early T cell development. Brg-deficient cells were blocked at each of the developmental transitions examined. Bcl-xL overexpression suppressed cell death without relieving the developmental blockades, leading to the accumulation of Brg-deleted cells that were unexpectedly cell cycle arrested. These defects resulted partly from the disruptions of pre-TCR and potentially Wnt signaling pathways controlling the expression of genes such as c-Kit and c-Myc critical for continued development. Our studies indicate that BAF complexes dynamically remodel chromatin to propel sequential developmental transitions in response to external signals.

Original languageEnglish
Pages (from-to)169-182
Number of pages14
JournalImmunity
Volume19
Issue number2
DOIs
Publication statusPublished - Aug 1 2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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