Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes
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 elongat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/116987 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1810982915479175168 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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. |
| author_sort | Cheng, Bo |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:38:13Z |
| format | Article |
| id | mit-1721.1/116987 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:38:13Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1169872022-09-30T21:58:38Z Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes 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. Massachusetts Institute of Technology. Department of Biology Young, Richard A 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) 2018-07-13T18:01:11Z 2018-07-13T18:01:11Z 2012-01 2011-08 2018-07-13T17:41:19Z Article http://purl.org/eprint/type/JournalArticle 1097-2765 1097-4164 http://hdl.handle.net/1721.1/116987 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 https://orcid.org/0000-0001-8855-8647 http://dx.doi.org/10.1016/j.molcel.2011.10.022 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | 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. Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title | Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title_full | Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title_fullStr | Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title_full_unstemmed | Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title_short | Functional Association of Gdown1 with RNA Polymerase II Poised on Human Genes |
| title_sort | functional association of gdown1 with rna polymerase ii poised on human genes |
| url | http://hdl.handle.net/1721.1/116987 https://orcid.org/0000-0001-8855-8647 |
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