PAF1 regulation of promoter-proximal pause release via enhancer activation

被引：89

作者：

Chen, Fei Xavier ^{[1
]}

Xie, Peng ^{[2
]}

Collings, Clayton K. ^{[1
]}

Cao, Kaixiang ^{[1
]}

Aoi, Yuki ^{[1
]}

Marshall, Stacy A. ^{[1
]}

Rendleman, Emily J. ^{[1
]}

Ugarenko, Michal ^{[1
]}

Ozark, Patrick A. ^{[1
]}

Zhang, Anda ^{[3
]}

Shiekhattar, Ramin ^{[3
]}

Smith, Edwin R. ^{[1
]}

Zhang, Michael Q. ^{[2
,4
,5
]}

Shilatifard, Ali ^{[1
,6
]}

机构：

[1] Northwestern Univ, Feinberg Sch Med, Dept Biochem & Mol Genet, Chicago, IL 60611 USA

[2] Univ Texas Dallas, Dept Biol Sci, Ctr Syst Biol, Richardson, TX 75080 USA

[3] Univ Miami, Miller Sch Med, Dept Human Genet, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA

[4] Tsinghua Univ, Bioinformat Div, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China

[5] Tsinghua Univ, Ctr Synthet & Syst Biol, TNLIST, Beijing 100084, Peoples R China

[6] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA

来源：

SCIENCE | 2017年 / 357卷 / 6357期

关键词：

RNA-POLYMERASE-II; TRANSCRIPTION ELONGATION; COMPLEX; DISTINCT; GENOME; GENES; ROLES; TEFB;

D O I：

10.1126/science.aan3269

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gene expression in metazoans is regulated by RNA polymerase II (Pol II) promoter-proximal pausing and its release. Previously, we showed that Pol II-associated factor 1 (PAF1) modulates the release of paused Pol II into productive elongation. Here, we found that PAF1 occupies transcriptional enhancers and restrains hyperactivation of a subset of these enhancers. Enhancer activation as the result of PAF1 loss releases Pol II from paused promoters of nearby PAF1 target genes. Knockout of PAF1-regulated enhancers attenuates the release of paused Pol II on PAF1 target genes without major interference in the establishment of pausing at their cognate promoters. Thus, a subset of enhancers can primarily modulate gene expression by controlling the release of paused Pol II in a PAF1-dependent manner.

引用

页码：1294 / 1298

页数：5

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