Journal article
Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes
Molecular cell, Vol.45(1), pp.38-50
01/13/2012
DOI: 10.1016/j.molcel.2011.10.022
PMCID: PMC3259526
PMID: 22244331
Abstract
Most human genes are loaded with promoter-proximally paused RNA polymerase II (Pol II) molecules that are poised for release into productive elongation by P-TEFb. We present evidence that Gdown1, the product of the POLR2M gene that renders Pol II responsive to Mediator, is involved in Pol II elongation control. During in vitro transcription, Gdown1 specifically blocked elongation stimulation by TFIIF, inhibited the termination activity of TTF2, and influenced pausing factors NELF and DSIF, but did not affect the function of TFIIS or the mRNA capping enzyme. Without P-TEFb, Gdown1 led to the production of stably paused polymerases in the presence of nuclear extract. Supporting these mechanistic insights, ChIP-Seq demonstrated that Gdown1 mapped over essentially all poised polymerases across the human genome. Our results establish that Gdown1 stabilizes poised polymerases while maintaining their responsiveness to P-TEFb and suggest that Mediator overcomes a Gdown1-mediated block of initiation by allowing TFIIF function.
Details
- Title: Subtitle
- Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes
- Creators
- Bo Cheng - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USATiandao Li - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USAPeter B Rahl - Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USATodd E Adamson - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USANicholas B Loudas - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USAJiannan Guo - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USAKatayoun Varzavand - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USAJeffrey J Cooper - Biochemistry Department, University of Iowa, Iowa City, IA 52242, USAXiaopeng Hu - Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USAAverell Gnatt - Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USARichard A Young - Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USADavid H Price - Molecular and Cellular Biology Program, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Molecular cell, Vol.45(1), pp.38-50
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.molcel.2011.10.022
- PMID
- 22244331
- PMCID
- PMC3259526
- ISSN
- 1097-2765
- eISSN
- 1097-4164
- Language
- English
- Date published
- 01/13/2012
- Academic Unit
- The University of Iowa Institute for Vision Research; Surgery; Biochemistry and Molecular Biology
- Record Identifier
- 9984024412402771
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