3 years ago

PAF1 regulation of promoter-proximal pause release via enhancer activation

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

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.

Publisher URL: http://science.sciencemag.org/cgi/content/short/357/6357/1294

DOI: 10.1126/science.aan3269

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