PAF1 regulation of promoter-proximal pause release via enhancer activation

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Enhancer Elements, Genetic*
  • Gene Knockout Techniques
  • Humans
  • Immediate-Early Proteins / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic*
  • Serpin E2 / genetics
  • Transcription Factors
  • Transcriptional Activation*
  • Up-Regulation


  • IER5 protein, human
  • Immediate-Early Proteins
  • Nuclear Proteins
  • PAF1 protein, human
  • SERPINE2 protein, human
  • Serpin E2
  • Transcription Factors