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首页> 外文期刊>Molecular and Cellular Biology >Histone Deacetylase 7 and FoxA1 in Estrogen-Mediated Repression of RPRM
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Histone Deacetylase 7 and FoxA1 in Estrogen-Mediated Repression of RPRM

机译：组蛋白脱乙酰基酶7和FoxA1在雌激素介导的RPRM抑制中。

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Activation of estrogen receptor α (ERα) results in both induction and repression of gene transcription; while mechanistic details of estrogen induction are well described, details of repression remain largely unknown. We characterized several ERα-repressed targets and examined in detail the mechanism for estrogen repression of Reprimo (RPRM), a cell cycle inhibitor. Estrogen repression of RPRM is rapid and robust and requires a tripartite interaction between ERα, histone deacetylase 7 (HDAC7), and FoxA1. HDAC7 is the critical HDAC needed for repression of RPRM; it can bind to ERα and represses ERα's transcriptional activity—this repression does not require HDAC7's deacetylase activity. We further show that the chromatin pioneer factor FoxA1, well known for its role in estrogen induction of genes, is recruited to the RPRM promoter, is necessary for repression of RPRM, and interacts with HDAC7. Like other FoxA1 recruitment sites, the RPRM promoter is characterized by H3K4me1/me2. Estrogen treatment causes decreases in H3K4me1/me2 and release of RNA polymerase II (Pol II) from the RPRM proximal promoter. Overall, these data implicate a novel role for HDAC7 and FoxA1 in estrogen repression of RPRM, a mechanism which could potentially be generalized to many more estrogen-repressed genes and hence be important in both normal physiology and pathological processes.
机译：雌激素受体α（ERα）的激活导致基因转录的诱导和抑制。尽管对雌激素诱导的机制细节已有很好的描述，但抑制的细节仍然未知。我们表征了几个ERα抑制的目标，并详细检查了细胞周期抑制剂Reprimo（RPRM）的雌激素抑制机制。 RPRM的雌激素抑制作用迅速且稳定，需要ERα，组蛋白脱乙酰基酶7（HDAC7）和FoxA1之间的三方相互作用。 HDAC7是抑制RPRM所需的关键HDAC。它可以与ERα结合并抑制ERα的转录活性-这种抑制作用不需要HDAC7的脱乙酰酶活性。我们进一步表明，以其在雌激素诱导基因中的作用而闻名的染色质先驱因子FoxA1被募集到RPRM启动子，是抑制RPRM所必需的，并与HDAC7相互作用。像其他FoxA1招聘网站一样，RPRM启动子的特征是H3K4me1 / me2。雌激素治疗会导致H3K4me1 / me2减少以及从RPRM近端启动子释放RNA聚合酶II（Pol II）。总体而言，这些数据暗示了HDAC7和FoxA1在RPRM的雌激素抑制中具有新的作用，该机制可能会推广到更多受雌激素抑制的基因，因此在正常生理和病理过程中均很重要。

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