Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo.
Tail and Kinase Modules Differently Regulate Core Mediator Recruitment and Function In Vivo.
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DOI：
10.1016/j.molcel.2016.09.002
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发表时间：
2016-11-03
期刊：
影响因子：
16
通讯作者：
Robert F
中科院分区：
文献类型：
--
作者：
Jeronimo C;Langelier MF;Bataille AR;Pascal JM;Pugh BF;Robert F
介体是一种高度保守的转录辅激活因子，分为四个模块，即尾，中间，头和激酶（CKM）。以前的工作表明，尾巴和CKM的监管作用，但这些活动的综合模型是缺乏的。在这里，我们分析了介体亚基在野生型和突变型酵母细胞中的基因组分布，其中RNA聚合酶II启动子逃逸被阻断，允许检测瞬时介体形式。我们发现，虽然所有的模块被招募到上游激活区（UAS），组装的调解人内的前启动复合物是伴随着释放CKM。有趣的是，我们的数据表明，CKM调节介体-UAS相互作用，而不是介体-启动子关联。此外，虽然尾是必需的介体募集到UAS，无尾介体仍然与核心启动子相互作用。总的来说，我们的数据表明，调解人的基本功能是介导的头部和中间的核心启动子，而尾部和CKM发挥调节作用。Jeronimo等人描述了一个中介子模块与基因相互作用的动态模型。CKM负调节介体-UAS相互作用，并在介体整合到PIC中时与介体分离。Tailless Mediator通过替代途径整合PIC。
Mediator is a highly conserved transcriptional coactivator organized into four modules, namely Tail, Middle, Head, and Kinase (CKM). Previous work suggests regulatory roles for Tail and CKM, but an integrated model for these activities is lacking. Here, we analyzed the genome-wide distribution of Mediator subunits in wild-type and mutant yeast cells in which RNA polymerase II promoter escape is blocked, allowing detection of transient Mediator forms. We found that although all modules are recruited to upstream activated regions (UAS), assembly of Mediator within the pre-initiation complex is accompanied by the release of CKM. Interestingly, our data show that CKM regulates Mediator-UAS interaction rather than Mediator-promoter association. In addition, although Tail is required for Mediator recruitment to UAS, Tailless Mediator nevertheless interacts with core promoters. Collectively, our data suggest that the essential function of Mediator is mediated by Head and Middle at core promoters, while Tail and CKM play regulatory roles. Jeronimo et al. describe a dynamic model for the interaction of Mediator modules with genes. CKM negatively regulates Mediator-UAS interactions and dissociates from Mediator upon integration of Mediator into the PIC. Tailless Mediator integrates PIC through an alternative pathway.
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