PAF1 regulation of promoter-proximal pause release via enhancer activation

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.

Source: ScienceNOW - September 21, 2017 Category: Science Authors: 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. Tags: Biochemistry, Development reports Source Type: news