Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
Reciprocal regulation of CD4/CD8 expression by SWI/SNF-like BAF complexes
复制标题
DOI：
10.1038/nature00876
复制
发表时间：
2002-07-11
期刊：
影响因子：
64.8
通讯作者：
Crabtree, GR
中科院分区：
文献类型：
--
作者：
Chi, TH;Wan, M;Crabtree, GR
胸腺发育产生两个表达 CD4 或 CD8 共受体的 T 细胞亚谱系，分别协助抗体产生和介导细胞杀伤。相互排斥的共受体表达的机制仍然不明确(1,2)。我们发现，BAF57（哺乳动物 SWI/SNF 样染色质重塑 BAF 复合物的 DNA 结合亚基）BAF57 的高迁移率基团 (HMG) 结构域或 BAF 复合物 ATP 酶亚基 Brg 中的突变会损害 CD4 沉默和 CD8 激活。 Brg 单倍体不足以激活 CD8，但不能激活 CD4 沉默，而 BAF57 突变优先损害 CD4 沉默，表明染色质重塑的目标和亚基特异性机制。 BAF 复合物直接结合 CD4 沉默子，但 BAF57 HMG 结构域对于将 BAF 复合物束缚到体内 CD4 沉默子或其他染色质位点，或体外重塑重组模板来说是可有可无的 (3,4)，这表明体内染色质重塑需要 HMG 依赖性 DNA 弯曲。这些结果表明，BAF 复合物通过相互调节谱系特异性基因来促进谱系分叉，这让人想起酵母 SWI/SNF 复合物在介导交配类型转换中的作用 (5,6)
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 defined(1,2). We find that mutations in the high mobility group (HMG) domain of BAF57-a DNA-binding subunit of the mammalian SWI/SNF-like chromatin-remodelling BAF complexesor in the BAF complex ATPase subunit Brg, impair both CD4 silencing and CD8 activation. Brg is haploinsufficient for CD8 activation, but not for CD4 silencing, whereas BAF57 mutations preferentially impair CD4 silencing, pointing to target- and subunit-specific mechanisms of chromatin remodelling. BAF complexes directly bind the CD4 silencer, but the BAF57 HMG domain is dispensable for tethering BAF complexes to the CD4 silencer or other chromatin loci in vivo, or for remodelling reconstituted templates in vitro(3,4), suggesting that chromatin remodelling in vivo requires HMG-dependent DNA bending. These results indicate that BAF complexes contribute to lineage bifurcation by reciprocally regulating lineage-specific genes, reminiscent of the role of the yeast SWI/SNF complex in mediating mating-type switching(5,6)