Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development.
Fiche publication
Date publication
août 2003
Journal
Immunity
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Chi TH, Wan M, Lee PP, Akashi K, Metzger D, Chambon P, Wilson CB, Crabtree GR
Lien Pubmed
Résumé
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.
Mots clés
Adenosine Triphosphatases, metabolism, Animals, Cell Cycle, Cell Differentiation, Chromatin, metabolism, DNA Helicases, Genes, myc, Mice, Mice, Knockout, Mice, Transgenic, Models, Immunological, Nuclear Proteins, deficiency, Nucleic Acid Denaturation, Proto-Oncogene Proteins c-bcl-2, metabolism, Proto-Oncogene Proteins c-kit, metabolism, Signal Transduction, T-Lymphocytes, cytology, Transcription Factors, deficiency, bcl-X Protein
Référence
Immunity. 2003 Aug;19(2):169-82