Journal
IMMUNITY
Volume 19, Issue 2, Pages 169-182Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(03)00199-7
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Funding
- NCI NIH HHS [CA39612] Funding Source: Medline
- NICHD NIH HHS [HD39454] Funding Source: Medline
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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 Writ 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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