Histone H2A.Z is essential for estrogen receptor signaling
Histone H2A.Z is essential for estrogen receptor signaling
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DOI：
10.1101/gad.1787109
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发表时间：
2009-07-01
影响因子：
10.5
通讯作者：
Gaudreau, Luc
中科院分区：
文献类型：
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作者：
Gevry, Nicolas;Hardy, Sara;Gaudreau, Luc
已显示将H2A.Z掺入失活启动子的染色质中可使基因稳定以用于其表达。在这里，我们提供了强有力的证据表明，H2A.Z被纳入到启动子区的雌激素受体（ER α）靶基因只有在基因诱导，并在一个循环模式。此外，人H2 A. Z-沉积复合物p400的成员也遵循与H2 A. Z相同的基因募集动力学。重要的是，H2A.Z或p400的细胞耗竭导致雌激素信号传导的严重缺陷，包括雌激素特异性细胞增殖的丧失。我们发现，TFF 1启动子染色质内的H2 A. Z的掺入允许核小体沿沿着DNA平移轴采取优先位置。最后，我们提供的证据表明，H2A.Z是必不可少的，让雌激素反应增强功能。总之，我们的研究结果提供了强有力的机制洞察H2A.Z如何调节ER α介导的基因表达，并提供了H2 A.Z-p400和ER α依赖的基因调控和增强子功能之间的新联系。
Incorporation of H2A.Z into the chromatin of inactive promoters has been shown to poise genes for their expression. Here we provide strong evidence that H2A.Z is incorporated into the promoter regions of estrogen receptor (ER alpha) target genes only upon gene induction, and that, in a cyclic pattern. Moreover, members of the human H2A.Z-depositing complex, p400, also follow the same gene recruitment kinetics as H2A.Z. Importantly, cellular depletion of H2A.Z or p400 leads to a severe defect in estrogen signaling, including loss of estrogen-specific cell proliferation. We find that incorporation of H2A.Z within TFF1 promoter chromatin allows nucleosomes to adopt preferential positions along the DNA translational axis. Finally, we provide evidence that H2A.Z is essential to allow estrogen-responsive enhancer function. Taken together, our results provide strong mechanistic insight into how H2A.Z regulates ER alpha-mediated gene expression and provide a novel link between H2A.Z-p400 and ER alpha-dependent gene regulation and enhancer function.