Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell. 2015 Aug 27;162(5):1003-15. doi: 10.1016/j.cell.2015.07.042. Epub 2015 Aug 13.

PAF1, a Molecular Regulator of Promoter-Proximal Pausing by RNA Polymerase II.

Author information

1
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Chicago, IL 60611, USA.
2
Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1501 NW 10(th) Avenue, Miami, FL 33136, USA.
3
Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, 320 E. Superior Street, Chicago, IL 60611, USA; Stowers Institute for Medical Research, 1000 East 50(th) Street, Kansas City, MO 64110, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA. Electronic address: ash@northwestern.edu.

Abstract

The control of promoter-proximal pausing and the release of RNA polymerase II (Pol II) is a widely used mechanism for regulating gene expression in metazoans, especially for genes that respond to environmental and developmental cues. Here, we identify that Pol-II-associated factor 1 (PAF1) possesses an evolutionarily conserved function in metazoans in the regulation of promoter-proximal pausing. Reduction in PAF1 levels leads to an increased release of paused Pol II into gene bodies at thousands of genes. PAF1 depletion results in increased nascent and mature transcripts and increased levels of phosphorylation of Pol II's C-terminal domain on serine 2 (Ser2P). These changes can be explained by the recruitment of the Ser2P kinase super elongation complex (SEC) effecting increased release of paused Pol II into productive elongation, thus establishing PAF1 as a regulator of promoter-proximal pausing by Pol II.

PMID:
26279188
PMCID:
PMC4679144
DOI:
10.1016/j.cell.2015.07.042
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center