PAF1 regulation of promoter-proximal pause release via enhancer activation

Fei Xavier Chen, Peng Xie, Clayton K. Collings, Kaixiang Cao, Yuki Aoi, Stacy A. Marshall, Emily J. Rendleman, Michal Ugarenko, Patrick A. Ozark, Anda Zhang, Ramin Shiekhattar, Edwin R. Smith, Michael Q. Zhang, Ali Shilatifard

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26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1294-1298
Number of pages5
JournalScience
Volume357
Issue number6357
DOIs
StatePublished - Sep 22 2017

ASJC Scopus subject areas

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    Chen, F. X., Xie, P., Collings, C. K., Cao, K., Aoi, Y., Marshall, S. A., Rendleman, E. J., Ugarenko, M., Ozark, P. A., Zhang, A., Shiekhattar, R., Smith, E. R., Zhang, M. Q., & Shilatifard, A. (2017). PAF1 regulation of promoter-proximal pause release via enhancer activation. Science, 357(6357), 1294-1298. https://doi.org/10.1126/science.aan3269