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首页> 外文期刊>Molecular and Cellular Biology >Med25 Is Required for RNA Polymerase II Recruitment to Specific Promoters, Thus Regulating Xenobiotic and Lipid Metabolism in Human Liver
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Med25 Is Required for RNA Polymerase II Recruitment to Specific Promoters, Thus Regulating Xenobiotic and Lipid Metabolism in Human Liver

机译：Med25是RNA聚合酶II招募至特定启动子所必需的，从而调节人肝中的异种生物和脂质代谢

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Hepatocyte nuclear factor 4α (HNF4α) controls the expression of many critical metabolic pathways, and the Mediator complex occupies a central role in recruiting RNA polymerase II (Pol II) to these gene promoters. An impaired transcriptional HNF4α network in human liver is responsible for many pathological conditions, such as altered drug metabolism, fatty liver, and diabetes. Here, we report that Med25, an associated member of the Mediator complex, is required for the association of HNF4α with Mediator, its several cofactors, and RNA Pol II. Further, increases and decreases in endogenous Med25 levels are reflected in the composition of the transcriptional complex, Pol II recruitment, and the expression of HNF4α-bound target genes. A novel feature of Med25 is that it imparts “selectivity.” Med25 affects only a significant subset of HNF4α target genes that selectively regulate drug and lipid metabolism. These results define a role for Med25 and the Mediator complex in the regulation of xenobiotic metabolism and lipid homeostasis.
机译：肝细胞核因子4α（HNF4α）控制着许多关键代谢途径的表达，介导复合物在将RNA聚合酶II（Pol II）募集到这些基因启动子中起着核心作用。人肝中转录HNF4α网络受损会导致许多病理状况，例如药物代谢改变，脂肪肝和糖尿病。在这里，我们报告说Med25是介体复合物的关联成员，对于HNF4α与介体，其几个辅因子和RNA Pol II的结合是必需的。此外，内源性Med25水平的升高和降低反映在转录复合物的组成，Pol II募集和HNF4α结合的靶基因的表达上。 Med25的一个新颖功能是赋予“选择性”。 Med25仅影响选择性调节药物和脂质代谢的HNF4α靶基因的重要子集。这些结果定义了Med25和介体复合物在异生物素代谢和脂质体内稳态调节中的作用。

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