Battaglioli Elena, Andrés Maria E, Rose Dave W, Chenoweth Josh G, Rosenfeld Michael G, Anderson Mary E, Mandel Gail
Department of Neurobiology and Behavior, Howard Hughes Medical Institute, State University of New York, Stony Brook, NY 11794, USA.
J Biol Chem. 2002 Oct 25;277(43):41038-45. doi: 10.1074/jbc.M205691200. Epub 2002 Aug 20.
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 RE1 reporter genes. Together, our data suggest that ATP-dependent chromatin remodeling, as well as histone deacetylation, is needed for REST-mediated repression.
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介导的抑制作用需要组蛋白去乙酰化酶活性，并且去乙酰化酶的募集是由两个共抑制因子Sin3A和CoREST介导的。在本研究中，我们表明CoREST中的一个抑制结构域与hSWI.SNF复合物的一个组分BRG1相关因子（BAF）57相互作用。在体内，BAF57占据神经元钠通道基因（Nav1.2）启动子，并且靶向该基因需要REST。除了BAF57之外，hSWI.SNF复合物的其他成员ATP酶BRG1和BAF170也存在于REST.CoREST抑制复合物中。向大鼠1成纤维细胞显微注射针对BRG1、BAF57或BAF170的特异性抗体可解除对RE1报告基因的抑制。我们的数据共同表明，REST介导的抑制作用需要ATP依赖的染色质重塑以及组蛋白去乙酰化。
