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首页> 外文期刊>Molecular and Cellular Biology >BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation
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BRG-1 Is Recruited to Estrogen-Responsive Promoters and Cooperates with Factors Involved in Histone Acetylation

机译：BRG-1被招募为雌激素反应性促进剂，并与组蛋白乙酰化相关的因子协同作用

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Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER–BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.
机译：几种介导核受体活化的因素也改变了染色质的化学和结构组成。这一类群中最突出的是类固醇受体共激活因子1（SRC-1）家族，该家族与激动剂结合的核受体相互作用，从而将它们与多功能转录共调节因子（如CREB结合蛋白（CBP），p300和PCAF）偶联，其中具有有效的组蛋白乙酰转移酶活性。此外，参与染色质结构重塑的包括梵天相关基因1（BRG-1）在内的其他因素也介导了核受体对激素依赖性转录激活的作用。在这里，我们提供证据表明，这两种不同的共激活机制可能以协作方式起作用。我们证明了由雌激素受体（ER）的转录激活需要功能性BRG-1，并且由SRC-1或CBP共同激活的雌激素信号是BRG-1依赖性的。我们发现，响应雌激素，ER募集了BRG-1，从而以与组蛋白乙酰化同时发生的方式将BRG-1靶向雌激素响应基因的启动子。最后，我们证明了BRG-1介导的ER信号共激活受细胞内组蛋白乙酰化状态的调节。曲古抑菌素A对组蛋白脱乙酰基的抑制作用显着增加了BRG-1介导的ER信号共激活，而组蛋白脱乙酰基酶1的过表达则逆转了这种增加。 –BRG-1将BRG-1偶联至雌激素反应性启动子位点的染色质区域，并促进其他募集因子改变染色质乙酰化状态的活性。

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