Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes

作者: Tian H. Chi , Mimi Wan , Keji Zhao , Ichiro Taniuchi , Lei Chen

DOI: 10.1038/NATURE00876

关键词: Cell killingGeneSWI/SNFGene silencingGene expressionProtein subunitCell biologyChromatinGeneticsHigh-mobility groupBiology

摘要: Thymic development produces two sub-lineages of T cells expressing either CD4 or CD8 co-receptors that assist antibody production and mediate cell killing, respectively. The mechanisms for mutually exclusive co-receptor expression remain poorly defined1,2. We find mutations in the high mobility group (HMG) domain BAF57—a DNA-binding subunit mammalian SWI/SNF-like chromatin-remodelling BAF complexes—or complex ATPase Brg, impair both silencing activation. Brg is haploinsufficient activation, but not silencing, whereas BAF57 preferentially pointing to target- subunit-specific chromatin remodelling. complexes directly bind silencer, HMG dispensable tethering silencer other loci vivo, remodelling reconstituted templates vitro3,4, suggesting vivo requires HMG-dependent DNA bending. These results indicate contribute lineage bifurcation by reciprocally regulating lineage-specific genes, reminiscent role yeast SWI/SNF mediating mating-type switching5,6.

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