Targeting of SWI/SNF chromatin remodelling complexes to estrogen-responsive genes

Targeting of SWI/SNF chromatin remodelling complexes to estrogen-responsive genes
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DOI:
10.1093/emboj/cdf412
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发表时间:
2002-08-01
期刊:
影响因子:
11.4
通讯作者:
Parker, MG
Parker, MG
中科院分区:
生物学1区
文献类型:
--
作者:
Belandia, B;Orford, RL;Parker, MG

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SWI/SNF复合物是ATP依赖的染色质重塑酶,在酵母和高等真核生物中参与基因表达的调节。BRG 1是哺乳动物SWI/SNF复合物中的催化亚基,是雌激素受体转录激活所必需的,但该复合物被募集到雌激素靶基因的机制尚不清楚。在这里,我们已经确定了雌激素受体和BAF 57,一个亚基只存在于哺乳动物SWI/SNF复合物,这是刺激雌激素,需要一个功能性的结合域和DNA结合区的受体之间的相互作用。我们还发现了p160家族的共激活因子和BAF 57之间的额外的相互作用,并证明了p160共激活因子增强雌激素受体转录的能力依赖于转染细胞中的BAF 57。此外,染色质免疫沉淀试验表明,BAF 57被招募到雌激素反应启动子,pS2,在配体依赖性的方式。这些结果表明,募集SWI/SNF复合物的雌激素靶基因的机制之一是通过BAF 57。
SWI/SNF complexes are ATP-dependent chromatin remodelling enzymes that have been implicated in the regulation of gene expression in yeast and higher eukaryotes. BRG1, a catalytic subunit in the mammalian SWI/SNF complex, is required for transcriptional activation by the estrogen receptor, but the mechanisms by which the complex is recruited to estrogen target genes are unknown. Here, we have identified an interaction between the estrogen receptor and BAF57, a subunit present only in mammalian SWI/SNF complexes, which is stimulated by estrogen and requires both a functional hormone-binding domain and the DNA-binding region of the receptor. We also found an additional interaction between the p160 family of coactivators and BAF57 and demonstrate that the ability of p160 coactivators to potentiate transcription by the estrogen receptor is dependent on BAF57 in transfected cells. Moreover, chromatin immunoprecipitation assays demonstrated that BAF57 is recruited to the estrogen-responsive promoter, pS2, in a ligand-dependent manner. These results suggest that one of the mechanisms for recruiting SWI/SNF complexes to estrogen target genes is by means of BAF57.