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Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes

Author(s)
Cheng, Bo; Li, Tiandao; Rahl, Peter B.; Adamson, Todd E.; Loudas, Nicholas B.; Guo, Jiannan; Varzavand, Katayoun; Cooper, Jeffrey J.; Hu, Xiaopeng; Gnatt, Averell; Price, David H.; Young, Richard A.; ... Show more Show less
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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.
Date issued
2012-01
URI
http://hdl.handle.net/1721.1/116987
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Molecular Cell
Publisher
Elsevier
Citation
Cheng, Bo et al. “Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes.” Molecular Cell 45, 1 (January 2012): 38–50 © 2012 Elsevier Inc
Version: Author's final manuscript
ISSN
1097-2765
1097-4164

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