Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements
Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements
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DOI：
10.1128/mcb.00920-10
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发表时间：
2011-04-01
影响因子：
5.3
通讯作者：
Pazin, Michael J.
中科院分区：
文献类型：
--
作者：
De, Supriyo;Wurster, Andrea L.;Pazin, Michael J.
辅助性T细胞的分化和激活需要特定的转录程序伴随着染色质结构的变化。然而，很少有人知道染色质重塑酶负责。我们进行了全基因组分析，以确定BRG 1结合的一般原则，然后分析特定基因，以确定这些一般规则是否是关键T细胞基因的典型特征。我们发现重塑蛋白BRG 1的结合是由谱系和激活信号编程的。BRG 1结合与蛋白质编码和microRNA（miRNA）基因的基因活性呈正相关。BRG1结合发现在启动子和远端区域，包括新的和以前验证的远端调控元件。远端BRG1结合与表达相关，Gata3基因座中的新远端位点具有增强子样活性，表明BRG1在远距离基因调控中的一般作用。在缺乏STAT6（一种调节谱系特异性基因的转录因子）的细胞中，Gata3远端位点的BRG 1募集受损。总之，这些发现表明，BRG1解释分化和激活信号，并在基因调控，染色质结构和细胞命运中发挥因果作用。我们的研究结果表明，BRG1结合是一个有用的标记，用于识别蛋白质编码和miRNA基因中的活性顺式调控区域。
T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes.