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PAF1 regulation of promoter-proximal pause release via enhancer activation

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Science  22 Sep 2017:
Vol. 357, Issue 6357, pp. 1294-1298
DOI: 10.1126/science.aan3269

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Multitalented enhancers

Productive transcription from DNA demands initiation, elongation, and termination. Enhancers are DNA sequences that loop with promoters to initiate transcription. Chen et al. show that enhancers also regulate gene expression by modulating transcription elongation. PAF1, a RNA polymerase II–associated factor, sits on enhancers. This prevents the full activation of the enhancer required for the release of paused polymerase at promoters to achieve successful transcription elongation.

Science, this issue p. 1294

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.

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