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.
Original language | English (US) |
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Pages (from-to) | 1294-1298 |
Number of pages | 5 |
Journal | Science |
Volume | 357 |
Issue number | 6357 |
DOIs | |
State | Published - Sep 22 2017 |
Funding
We thank all the members of the Shilatifard laboratory, J. Yu, J. Crispino, J. Wang, and D. Taatjes for helpful discussions during the course of this work; I. Cheeseman for the gift of the OsTIR1-expressing DLD-1 cell line; M. Kanemaki for the gift of the pMK286 (mAID-Neo) and pMK287 (mAID-Hygro) plasmids; M. Mendillo and S. Takagishi for suggestions about CRISPR/Cas9; and L. Shilatifard for editorial assistance. ChIP-seq, RNA-seq, and 4C-seq data have been deposited at the Gene Expression Omnibus (GEO) under accession number GSE97527. Supported by NIH grant MH102616 and Natural Science Foundation of China grant 31671384 (M.Q.Z.); NIH grant CA211428 (E.R.S.); NIH grants GM078455 and GM105754 and the University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center (R.S.); a JSPS Research Fellowship for Young Scientists (Y.A.); a Eugene McDermott Graduate Fellowship (P.X.); and a Robert H. Lurie Comprehensive Cancer Center–Lefkofsky Family Foundation/Liz and Eric Lefkofsky Innovation Research Award (A.S.). Transcriptional elongation studies in the Shilatifard laboratory are supported by National Cancer Institute grant CA214035 (A.S.).
ASJC Scopus subject areas
- General