PAF1 Regulation of Promoter-proximal Pause Release Via Enhancer Activation

Overview

Journal Science

Specialty Science

Date 2017 Sep 2

PMID 28860207

Citations 65

Authors

Fei Xavier Chen

Peng Xie

Clayton K Collings

Kaixiang Cao

Yuki Aoi

Stacy A Marshall

Emily J Rendleman

Michal Ugarenko

Patrick A Ozark

Anda Zhang

Ramin Shiekhattar

Edwin R Smith

Michael Q Zhang

Ali Shilatifard

Affiliations

Soon will be listed here.

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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References

Heintzman N, Stuart R, Hon G, Fu Y, Ching C, Hawkins R . Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007; 39(3):311-8. DOI: 10.1038/ng1966. View

Winter G, Mayer A, Buckley D, Erb M, Roderick J, Vittori S . BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017; 67(1):5-18.e19. PMC: 5663500. DOI: 10.1016/j.molcel.2017.06.004. View

McNamara R, Reeder J, McMillan E, Bacon C, McCann J, DOrso I . KAP1 Recruitment of the 7SK snRNP Complex to Promoters Enables Transcription Elongation by RNA Polymerase II. Mol Cell. 2016; 61(1):39-53. PMC: 4714561. DOI: 10.1016/j.molcel.2015.11.004. View

Holland A, Fachinetti D, Han J, Cleveland D . Inducible, reversible system for the rapid and complete degradation of proteins in mammalian cells. Proc Natl Acad Sci U S A. 2012; 109(49):E3350-7. PMC: 3523849. DOI: 10.1073/pnas.1216880109. View

Li B, Dewey C . RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinformatics. 2011; 12:323. PMC: 3163565. DOI: 10.1186/1471-2105-12-323. View

Lin C, Garrett A, De Kumar B, Smith E, Gogol M, Seidel C . Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC). Genes Dev. 2011; 25(14):1486-98. PMC: 3143939. DOI: 10.1101/gad.2059211. View

Gibson B, Zhang Y, Jiang H, Hussey K, Shrimp J, Lin H . Chemical genetic discovery of PARP targets reveals a role for PARP-1 in transcription elongation. Science. 2016; 353(6294):45-50. PMC: 5540732. DOI: 10.1126/science.aaf7865. View

Cao K, Collings C, Marshall S, Morgan M, Rendleman E, Wang L . SET1A/COMPASS and shadow enhancers in the regulation of homeotic gene expression. Genes Dev. 2017; 31(8):787-801. PMC: 5435891. DOI: 10.1101/gad.294744.116. View

Lagha M, Bothma J, Esposito E, Ng S, Stefanik L, Tsui C . Paused Pol II coordinates tissue morphogenesis in the Drosophila embryo. Cell. 2013; 153(5):976-87. PMC: 4257494. DOI: 10.1016/j.cell.2013.04.045. View

10.

Rahl P, Lin C, Seila A, Flynn R, McCuine S, Burge C . c-Myc regulates transcriptional pause release. Cell. 2010; 141(3):432-45. PMC: 2864022. DOI: 10.1016/j.cell.2010.03.030. View

11.

Natsume T, Kiyomitsu T, Saga Y, Kanemaki M . Rapid Protein Depletion in Human Cells by Auxin-Inducible Degron Tagging with Short Homology Donors. Cell Rep. 2016; 15(1):210-218. DOI: 10.1016/j.celrep.2016.03.001. View

12.

Gardini A, Baillat D, Cesaroni M, Hu D, Marinis J, Wagner E . Integrator regulates transcriptional initiation and pause release following activation. Mol Cell. 2014; 56(1):128-139. PMC: 4292851. DOI: 10.1016/j.molcel.2014.08.004. View

13.

Yang Y, Li W, Hoque M, Hou L, Shen S, Tian B . PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation. PLoS Genet. 2016; 12(1):e1005794. PMC: 4713055. DOI: 10.1371/journal.pgen.1005794. View

14.

Creyghton M, Cheng A, Welstead G, Kooistra T, Carey B, Steine E . Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc Natl Acad Sci U S A. 2010; 107(50):21931-6. PMC: 3003124. DOI: 10.1073/pnas.1016071107. View

15.

Whyte W, Orlando D, Hnisz D, Abraham B, Lin C, Kagey M . Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013; 153(2):307-19. PMC: 3653129. DOI: 10.1016/j.cell.2013.03.035. View

16.

Ramirez F, Ryan D, Gruning B, Bhardwaj V, Kilpert F, Richter A . deepTools2: a next generation web server for deep-sequencing data analysis. Nucleic Acids Res. 2016; 44(W1):W160-5. PMC: 4987876. DOI: 10.1093/nar/gkw257. View

17.

Zhang Y, Liu T, Meyer C, Eeckhoute J, Johnson D, Bernstein B . Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9(9):R137. PMC: 2592715. DOI: 10.1186/gb-2008-9-9-r137. View

18.

Tomson B, Arndt K . The many roles of the conserved eukaryotic Paf1 complex in regulating transcription, histone modifications, and disease states. Biochim Biophys Acta. 2012; 1829(1):116-26. PMC: 3541448. DOI: 10.1016/j.bbagrm.2012.08.011. View

19.

Cheng B, Li T, Rahl P, Adamson T, Loudas N, Guo J . Functional association of Gdown1 with RNA polymerase II poised on human genes. Mol Cell. 2012; 45(1):38-50. PMC: 3259526. DOI: 10.1016/j.molcel.2011.10.022. View

20.

Yu M, Yang W, Ni T, Tang Z, Nakadai T, Zhu J . RNA polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA polymerase II. Science. 2015; 350(6266):1383-6. PMC: 8729149. DOI: 10.1126/science.aad2338. View