PAF1 regulation of promoter-proximal pause release via enhancer activation

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

来源：Science, 2017, 357(6357): 1294-1298.

DOI：10.1126/science.aan3269

• RNA-POLYMERASE-II
• TRANSCRIPTION ELONGATION
• COMPLEX
• DISTINCT
• GENOME
• GENES
• ROLES
• TEFB

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.

• 出版日期2017-9-22
• 单位西北大学; 清华大学