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

Research paper by Fei Xavier FX Chen, Peng P Xie, Clayton K CK Collings, Kaixiang K Cao, Yuki Y Aoi, Stacy A SA Marshall, Emily J EJ Rendleman, Michal M Ugarenko, Patrick A PA Ozark, Anda A Zhang, Ramin R Shiekhattar, Edwin R ER Smith, Michael Q MQ Zhang, Ali A Shilatifard

Indexed on: 02 Sep '17Published on: 02 Sep '17Published in: Science


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.