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Science. 2017 Sep 22;357(6357):1294-1298. doi: 10.1126/science.aan3269. Epub 2017 Aug 31.

PAF1 regulation of promoter-proximal pause release via enhancer activation.

Author information

1
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
2
Department of Biological Sciences, Center for Systems Biology, University of Texas at Dallas, Richardson, TX 75080, USA.
3
Sylvester Comprehensive Cancer Center, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
4
MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China.
5
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. ash@northwestern.edu.
6
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Abstract

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.

PMID:
28860207
PMCID:
PMC6055228
DOI:
10.1126/science.aan3269
[Indexed for MEDLINE]
Free PMC Article

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