Functional association of Gdown1 with RNA polymerase II poised on human genes.
Functional association of Gdown1 with RNA polymerase II poised on human genes.
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GDown1与RNA聚合酶II的功能关联，该聚合酶II有证明在人类基因上。
DOI：
10.1016/j.molcel.2011.10.022
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发表时间：
2012-01-13
期刊：
影响因子：
16
通讯作者：
Price, David H.
中科院分区：
文献类型：
--
作者：
Cheng, Bo;Li, Tiandao;Rahl, Peter B.;Adamson, Todd E.;Loudas, Nicholas B.;Guo, Jiannan;Varzavand, Katayoun;Cooper, Jeffrey J.;Hu, Xiaopeng;Gnatt, Averell;Young, Richard A.;Price, David H.
大多数人类基因装载有启动子近端暂停的RNA聚合酶II（Pol II）分子，其准备通过P-TEFb释放到生产性延伸中。我们提出的证据表明，Gdown 1，蛋白质，使Pol II响应介质，参与Pol II的伸长控制。在体外转录试验中，Gdown 1特异性阻断TFIIF的延长刺激，抑制TTF 2的终止活性，并影响暂停因子NELF和DSIF，但不影响TFIIS或mRNA加帽酶的功能。在没有P-TEFb的情况下，Gdown 1导致在核提取物存在下稳定暂停的聚合酶的产生。支持这些机制的见解，ChIP-Seq证明Gdown 1映射到人类基因组中基本上所有的聚合酶。我们的研究结果表明，Gdown 1增加了稳定的聚合酶，同时保持其对P-TEFb的反应性，并表明介体克服了Gdown 1介导的阻断启动允许TFIIF功能。
Most human genes are loaded with promoter proximally paused RNA polymerase II (Pol II) molecules that are poised for release into productive elongation by P-TEFb. We present evidence that Gdown1, a protein that renders Pol II responsive to mediator, is involved in Pol II elongation control. During in vitro transcription assays Gdown1 specifically blocked elongation stimulation by TFIIF, inhibited the termination activity of TTF2, and influenced pausing factors NELF and DSIF, but did not affect the function of TFIIS or the mRNA capping enzyme. Without P-TEFb, Gdown1 led to the production of stably paused polymerases in the presence of nuclear extract. Supporting these mechanistic insights, ChIP-Seq demonstrated that Gdown1 mapped over essentially all poised polymerases across the human genome. Our results establish that Gdown1 increases the stability of poised polymerases while maintaining their responsiveness to P-TEFb and suggest that mediator overcomes a Gdown1-mediated block of initiation by allowing TFIIF function.
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