Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes
| Autor: | Todd E. Adamson, Tiandao Li, Richard A. Young, Nicholas B. Loudas, Peter B. Rahl, Averell Gnatt, Jiannan Guo, Jeffrey J. Cooper, David H. Price, Katayoun Varzavand, Bo Cheng, Xiaopeng Hu |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biology, Young, Richard A |
| Rok vydání: | 2012 |
| Předmět: |
0303 health sciences
Transcription Genetic biology 030302 biochemistry & molecular biology RNA polymerase II Cell Biology DSIF Molecular biology Article Cell biology Transcription Factors TFII 03 medical and health sciences Transcription (biology) biology.protein Humans Transcription factor II F RNA Polymerase II Transcription factor II D Molecular Biology Transcription factor RNA polymerase II holoenzyme Polymerase HeLa Cells 030304 developmental biology |
| Zdroj: | PMC |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2011.10.022 |
| Popis: | 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. National Human Genome Research Institute (U.S.) (Grant HG002668-05) |
| Databáze: | OpenAIRE |
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