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

Immunity. 2003 Aug;19(2):169-82. doi: 10.1016/s1074-7613(03)00199-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cell Cycle
  • Cell Differentiation
  • Chromatin / metabolism*
  • DNA Helicases
  • Genes, myc
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleic Acid Denaturation
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Signal Transduction
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • bcl-X Protein

Substances

  • Bcl2l1 protein, mouse
  • Chromatin
  • Nuclear Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Smarca2 protein, mouse
  • Transcription Factors
  • bcl-X Protein
  • Proto-Oncogene Proteins c-kit
  • Adenosine Triphosphatases
  • Smarca4 protein, mouse
  • DNA Helicases