c-Myc regulates transcriptional pause release.

c-Myc regulates transcriptional pause release.
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DOI:
10.1016/j.cell.2010.03.030
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发表时间:
2010-04-30
期刊:
影响因子:
64.5
通讯作者:
Young RA
Young RA
中科院分区:
生物学1区
文献类型:
--
作者:
Rahl PB;Lin CY;Seila AC;Flynn RA;McCuine S;Burge CB;Sharp PA;Young RA

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通过特定的DNA结合转录因子募集RNA聚合酶II(POL II)转录起始设备向启动子募集被很好地认为是基因表达的关键调节步骤。我们在这里报告说,启动子 - 抗暂停是Pol II在哺乳动物细胞中转录的一般特征,因此是发生基因表达调节的另一个步骤。这表明某些转录因子募集了转录设备为启动子,而另一些转录因子会影响启动子释放。确实,我们发现转录因子C-MYC是细胞增殖的关键调节剂,在其靶基因的pol II暂停释放而不是pol II募集中起着重要作用。我们讨论了这些结果对C-MYC扩增在人类癌症中的作用的含义。
Recruitment of the RNA Polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells, and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, while others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer.
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