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首页> 外文期刊>Molecular and Cellular Biology >The HSA Domain of BRG1 Mediates Critical Interactions Required for Glucocorticoid Receptor-Dependent Transcriptional Activation In Vivo
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The HSA Domain of BRG1 Mediates Critical Interactions Required for Glucocorticoid Receptor-Dependent Transcriptional Activation In Vivo

机译:BRG1的HSA域介导体内糖皮质激素受体依赖性转录激活所需的关键相互作用。

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The packaging of eukaryotic DNA into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. The mammalian SWI/SNF remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. BRG1 (or hBrm), the central ATPase of the human SWI/SNF complex, is a critical factor for the functional activity of nuclear receptor complexes. Analysis using BRG1/SNF2h chimeras suggests BRG1 may contain previously uncharacterized functional motifs important for SWI/SNF. To identify these regions, BRG1 truncation and deletion mutants were designed, characterized, and utilized in a series of assays to evaluate transcriptional activation and chromatin remodeling by the glucocorticoid receptor. We identified a domain within the N terminus of BRG1 that mediates critical protein interactions within SWI/SNF. We find the HSA domain of BRG1 is required to mediate the interaction with BAF250a/ARID1A and show this association is necessary for transcriptional activation from chromatin mouse mammary tumor virus or endogenous promoters in vivo. These studies suggest BAF250a is a necessary facilitator of BRG1-mediated chromatin remodeling required for SWI/SNF-dependent transcriptional activation.
机译:将真核DNA包装到染色质中可以通过阻碍转录所需的必需因子的结合而阻碍转录。哺乳动物SWI / SNF重塑复合物已显示可改变局部染色质结构并促进转录因子的募集。 BRG1(或hBrm)是人类SWI / SNF复合体的中央ATPase,是核受体复合体功能活动的关键因素。使用BRG1 / SNF2h嵌合体进行的分析表明,BRG1可能包含先前未表征的SWI / SNF重要功能基序。为了鉴定这些区域,设计,表征了BRG1截短和缺失突变体,并将其用于一系列测定,以评估糖皮质激素受体的转录激活和染色质重塑。我们在BRG1的N末端确定了一个域,该域介导SWI / SNF中的关键蛋白相互作用。我们发现BRG1的HSA结构域是介导与BAF250a / ARID1A相互作用所必需的,并且表明这种关联对于从染色质小鼠乳腺肿瘤病毒或体内内源性启动子转录激活是必需的。这些研究表明,BAF250a是SWI / SNF依赖性转录激活所需的BRG1介导的染色质重塑的必要促进剂。

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