c-Myc regulates transcriptional pause release

Recruitment of the RNA polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA-binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in...

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Main Authors: Rahl, Peter B., Lin, Charles Y., Flynn, Ryan A., McCuine, Scott, Sharp, Phillip A., Young, Richard A., White, Amy C., Burge, Christopher B
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2012
Online Access:http://hdl.handle.net/1721.1/72558
https://orcid.org/0000-0003-1465-1691
https://orcid.org/0000-0001-5013-0442
https://orcid.org/0000-0001-8855-8647
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author Rahl, Peter B.
Lin, Charles Y.
Flynn, Ryan A.
McCuine, Scott
Sharp, Phillip A.
Young, Richard A.
White, Amy C.
Burge, Christopher B
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Rahl, Peter B.
Lin, Charles Y.
Flynn, Ryan A.
McCuine, Scott
Sharp, Phillip A.
Young, Richard A.
White, Amy C.
Burge, Christopher B
author_sort Rahl, Peter B.
collection MIT
description Recruitment of the RNA polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA-binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, whereas others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer.
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spelling mit-1721.1/725582022-09-28T15:35:53Z c-Myc regulates transcriptional pause release Rahl, Peter B. Lin, Charles Y. Flynn, Ryan A. McCuine, Scott Sharp, Phillip A. Young, Richard A. White, Amy C. Burge, Christopher B Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Burge, Christopher B. Lin, Charles Y. Seila, Amy C. Flynn, Ryan A. Burge, Christopher B. Sharp, Phillip A. Young, Richard A. Recruitment of the RNA polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA-binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, whereas others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer. National Institutes of Health (U.S.) (Grant number RO1-HG002668) National Institutes of Health (U.S.) (Grant number RO1-GM34277) National Institutes of Health (U.S.) (Grant number RO1-CA133404) National Cancer Institute (U.S.) (Grant Number PO1- CA42063) National Cancer Institute (U.S.) Cancer Center Support Grant (Grant Number P30-CA14051) National Institutes of Health (U.S.) Postdoctoral Fellowship (5-F32-HD051190) 2012-09-07T12:54:06Z 2012-09-07T12:54:06Z 2010-04 2010-01 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/72558 Rahl, Peter B. et al. “c-Myc Regulates Transcriptional Pause Release.” Cell 141.3 (2010): 432–445. https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5013-0442 https://orcid.org/0000-0001-8855-8647 en_US http://dx.doi.org/10.1016/j.cell.2010.03.030 Cell Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Elsevier PMC
spellingShingle Rahl, Peter B.
Lin, Charles Y.
Flynn, Ryan A.
McCuine, Scott
Sharp, Phillip A.
Young, Richard A.
White, Amy C.
Burge, Christopher B
c-Myc regulates transcriptional pause release
title c-Myc regulates transcriptional pause release
title_full c-Myc regulates transcriptional pause release
title_fullStr c-Myc regulates transcriptional pause release
title_full_unstemmed c-Myc regulates transcriptional pause release
title_short c-Myc regulates transcriptional pause release
title_sort c myc regulates transcriptional pause release
url http://hdl.handle.net/1721.1/72558
https://orcid.org/0000-0003-1465-1691
https://orcid.org/0000-0001-5013-0442
https://orcid.org/0000-0001-8855-8647
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