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Immunity. 2003 Aug;19(2):169-82.

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

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Departments of Pathology and Developmental Biology, Howard Hughes Medical Institute, Stanford University Medical School, Palo Alto, California 94305, USA.


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.

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