REST repression of neuronal genes requires components of the hSWI-SNF complex
REST repression of neuronal genes requires components of the hSWI-SNF complex
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DOI：
10.1074/jbc.m205691200
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发表时间：
2002-10-25
影响因子：
4.8
通讯作者：
Mandel, G
中科院分区：
文献类型：
--
作者：
Battaglioli, E;Andrés, ME;Mandel, G
转录因子REST的一个功能是在非神经元细胞中阻断神经元表型特征的表达。先前的研究表明，REST介导的抑制需要组蛋白去乙酰基酶的活性，而去乙酰基酶的募集是由两个共抑制因子介导的，SIN3A和COREST。在这项研究中，我们证明了COREST中的一个抑制域与BRG1相关因子(BAF)57相互作用，BAF是hSWI-SNF复合体的一个组成部分。在体内，BAF57占据神经元性钠通道基因(Nav1.2)启动子，靶向该基因需要休息。除了BAF57，hSWI-SNF复合体的其他成员ATPase BRG1和BAF170也存在于REST-COST阻遏物复合体中。微量注射抗BRG1、BAF57或BAF170的特异性抗体到Rat1成纤维细胞中可以解除REI报告基因的抑制。综上所述，我们的数据表明，依赖于ATP的染色质重塑以及组蛋白去乙酰化是REST介导的抑制所必需的。
A function of the transcription factor REST is to block the expression of neuronal phenotypic traits in non-neuronal cells. Previous studies have shown that REST-mediated repression requires histone deacetylase activity and that recruitment of deacetylases is mediated by two co-repressors, Sin3A and CoREST. In this study, we show that a repressor domain in CoREST interacts with BRG1-associated factor (BAF) 57, a component of the hSWI-SNF complex. In vivo, BAF57 occupies the neuronal sodium channel gene (Nav1.2) promoter, and targeting to this gene requires REST. In addition to BAF57, the ATPase BRG1 and BAF170, other members of the hSWI-SNF complex, are also present in the REST-CoREST repressor complex. Microinjection of specific antibodies against BRG1, BAF57, or BAF170 into Rat1 fibroblasts relieves repression of REI reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression.