TFIIE orchestrates the recruitment of the TFIIH kinase module at promoter before release during transcription
TFIIE orchestrates the recruitment of the TFIIH kinase module at promoter before release during transcription
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DOI：
10.1038/s41467-019-10131-1
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发表时间：
2019-05-07
影响因子：
16.6
通讯作者：
Egly, Jean-Marc
中科院分区：
文献类型：
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作者：
Compe, Emmanuel;Genes, Carlos M.;Egly, Jean-Marc
在真核生物中，一般转录因子TFIIE和TFIIH在转录起始位点与RNA聚合酶II组装。然而，这些转录因子纳入preinitiation复合物，并协调它们的行动在RNA聚合酶II转录的机制仍然难以捉摸。在这里，我们表明，TFIIE α和TFIIE β亚基锚定TFIIH激酶模块（CAK）内的preinitiation复合物。此外，我们表明，虽然RNA聚合酶II磷酸化和DNA开放发生，CAK和TFIlE α从启动子释放。这种解离被ATP-γ S或CDK 7抑制剂THZ 1阻碍，但当XPB活性被消除时仍然发生。最后，我们表明，核心TFIIH和TFIIE β随后被删除，而延长因子，如DSIF招募。值得注意的是，这些早期的转录事件受到与发育障碍相关的TFIIE和TFIIH突变的影响。
In eukaryotes, the general transcription factors TFIIE and TFIIH assemble at the transcription start site with RNA Polymerase II. However, the mechanism by which these transcription factors incorporate the preinitiation complex and coordinate their action during RNA polymerase II transcription remains elusive. Here we show that the TFIlE alpha and TFIIE beta subunits anchor the TFIIH kinase module (CAK) within the preinitiation complex. In addition, we show that while RNA polymerase II phosphorylation and DNA opening occur, CAK and TFIlE alpha are released from the promoter. This dissociation is impeded by either ATP-gamma S or CDK7 inhibitor THZ1, but still occurs when XPB activity is abrogated. Finally, we show that the Core-TFIIH and TFIIE beta are subsequently removed, while elongation factors such as DSIF are recruited. Remarkably, these early transcriptional events are affected by TFIIE and TFIIH mutations associated with the developmental disorder, trichothiodystrophy.