Mediator-dependent recruitment of TFIIH modules in preinitiation complex
Mediator-dependent recruitment of TFIIH modules in preinitiation complex
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DOI：
10.1016/j.molcel.2008.06.021
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发表时间：
2008-08-08
期刊：
影响因子：
16
通讯作者：
Werner, Michel
中科院分区：
文献类型：
--
作者：
Esnault, Cyril;Ghavi-Helm, Yad;Werner, Michel
在体外，没有中介，一般转录因子（GTF）和RNA聚合酶11 （Pol II）在起始前复合物（PIC）中的关联以有序的方式发生。在这项工作中，我们探讨了中介在GTF向PIC募集中的体内功能。发现Med11 Mediator头亚基与Rad3 TFIIH亚基之间存在直接相互作用。我们探索了这种相互作用以及Med11与头部模块亚基Med17和Med22相互作用的重要性，发现破坏这些相互作用可能会不同地影响PIC中TFIIH、TFIIE和Pol II的募集。med11突变改变了TFIIH全基因组TFIIK激酶模块的启动子占用，也降低了Pol 11 CTD丝氨酸5的磷酸化。我们得出结论，调解人头部模块在TFIIH和TFIIE招募到PIC中起着关键作用。我们确定了PIC形成的步骤，表明了分支组装途径。
In vitro, without Mediator, the association of general transcription factors (GTF) and RNA polymerase 11 (Pol II) in preinitiation complexes (PIC) occurs in an orderly fashion. In this work, we explore the in vivo function of Mediator in GTF recruitment to PIC. A direct interaction between Med11 Mediator head subunit and Rad3 TFIIH subunit was identified. We explored the significance of this interaction and those of Med11 with head module subunits Med17 and Med22 and found that impairing these interactions could differentially affect the recruitment of TFIIH, TFIIE, and Pol II in the PIC. A med11 mutation that altered promoter occupancy by the TFIIK kinase module of TFIIH genome-wide also reduced Pol 11 CTD serine 5 phosphorylation. We conclude that the Mediator head module plays a critical role in TFIIH and TFIIE recruitment to the PIC. We identify steps in PIC formation that suggest a branched assembly pathway.