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Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II
The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001612/ https://www.ncbi.nlm.nih.gov/pubmed/27353326 http://dx.doi.org/10.1093/nar/gkw571 |
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author | Lu, Xiaodong Zhu, Xinxing Li, You Liu, Min Yu, Bin Wang, Yu Rao, Muhua Yang, Haiyang Zhou, Kai Wang, Yao Chen, Yanheng Chen, Meihua Zhuang, Songkuan Chen, Lin-Feng Liu, Runzhong Chen, Ruichuan |
author_facet | Lu, Xiaodong Zhu, Xinxing Li, You Liu, Min Yu, Bin Wang, Yu Rao, Muhua Yang, Haiyang Zhou, Kai Wang, Yao Chen, Yanheng Chen, Meihua Zhuang, Songkuan Chen, Lin-Feng Liu, Runzhong Chen, Ruichuan |
author_sort | Lu, Xiaodong |
collection | PubMed |
description | The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network. |
format | Online Article Text |
id | pubmed-5001612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50016122016-12-07 Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II Lu, Xiaodong Zhu, Xinxing Li, You Liu, Min Yu, Bin Wang, Yu Rao, Muhua Yang, Haiyang Zhou, Kai Wang, Yao Chen, Yanheng Chen, Meihua Zhuang, Songkuan Chen, Lin-Feng Liu, Runzhong Chen, Ruichuan Nucleic Acids Res Molecular Biology The association of DSIF and NELF with initiated RNA Polymerase II (Pol II) is the general mechanism for inducing promoter-proximal pausing of Pol II. However, it remains largely unclear how the paused Pol II is released in response to stimulation. Here, we show that the release of the paused Pol II is cooperatively regulated by multiple P-TEFbs which are recruited by bromodomain-containing protein Brd4 and super elongation complex (SEC) via different recruitment mechanisms. Upon stimulation, Brd4 recruits P-TEFb to Spt5/DSIF via a recruitment pathway consisting of Med1, Med23 and Tat-SF1, whereas SEC recruits P-TEFb to NELF-A and NELF-E via Paf1c and Med26, respectively. P-TEFb-mediated phosphorylation of Spt5, NELF-A and NELF-E results in the dissociation of NELF from Pol II, thereby transiting transcription from pausing to elongation. Additionally, we demonstrate that P-TEFb-mediated Ser2 phosphorylation of Pol II is dispensable for pause release. Therefore, our studies reveal a co-regulatory mechanism of Brd4 and SEC in modulating the transcriptional pause release by recruiting multiple P-TEFbs via a Mediator- and Paf1c-coordinated recruitment network. Oxford University Press 2016-08-19 2016-06-28 /pmc/articles/PMC5001612/ /pubmed/27353326 http://dx.doi.org/10.1093/nar/gkw571 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Molecular Biology Lu, Xiaodong Zhu, Xinxing Li, You Liu, Min Yu, Bin Wang, Yu Rao, Muhua Yang, Haiyang Zhou, Kai Wang, Yao Chen, Yanheng Chen, Meihua Zhuang, Songkuan Chen, Lin-Feng Liu, Runzhong Chen, Ruichuan Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title | Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title_full | Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title_fullStr | Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title_full_unstemmed | Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title_short | Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II |
title_sort | multiple p-tefbs cooperatively regulate the release of promoter-proximally paused rna polymerase ii |
topic | Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001612/ https://www.ncbi.nlm.nih.gov/pubmed/27353326 http://dx.doi.org/10.1093/nar/gkw571 |
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