c-Myc Regulates Transcriptional Pause Release

被引:1005
作者
Rahl, Peter B. [1 ]
Lin, Charles Y. [1 ,2 ]
Seila, Amy C. [3 ]
Flynn, Ryan A. [3 ]
McCuine, Scott [1 ]
Burge, Christopher B. [2 ]
Sharp, Phillip A. [2 ,3 ]
Young, Richard A. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02142 USA
[3] MIT, Koch Inst, Cambridge, MA 02142 USA
基金
美国国家卫生研究院;
关键词
RNA-POLYMERASE-II; EMBRYONIC STEM-CELLS; HEAT-SHOCK GENES; INHIBITS P-TEFB; IN-VIVO; TERMINAL DOMAIN; DROSOPHILA-MELANOGASTER; PRODUCTIVE ELONGATION; SELF-RENEWAL; PROCESSING FACTORS;
D O I
10.1016/j.cell.2010.03.030
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, whereas 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.
引用
收藏
页码:432 / 445
页数:14
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