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CDK9-dependent RNA polymerase II pausing controls transcription initiation
Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a ‘multi-omics’ approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669633/ https://www.ncbi.nlm.nih.gov/pubmed/28994650 http://dx.doi.org/10.7554/eLife.29736 |
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author | Gressel, Saskia Schwalb, Björn Decker, Tim Michael Qin, Weihua Leonhardt, Heinrich Eick, Dirk Cramer, Patrick |
author_facet | Gressel, Saskia Schwalb, Björn Decker, Tim Michael Qin, Weihua Leonhardt, Heinrich Eick, Dirk Cramer, Patrick |
author_sort | Gressel, Saskia |
collection | PubMed |
description | Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a ‘multi-omics’ approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells (‘pause-initiation limit’). We further engineer a human cell line to allow for specific and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release. CDK9 activity decreases the pause duration but also increases the productive initiation frequency. This shows that CDK9 stimulates release of paused polymerase and activates transcription by increasing the number of transcribing polymerases and thus the amount of mRNA synthesized per time. CDK9 activity is also associated with long-range chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to regulate transcription. |
format | Online Article Text |
id | pubmed-5669633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-56696332017-11-06 CDK9-dependent RNA polymerase II pausing controls transcription initiation Gressel, Saskia Schwalb, Björn Decker, Tim Michael Qin, Weihua Leonhardt, Heinrich Eick, Dirk Cramer, Patrick eLife Computational and Systems Biology Gene transcription can be activated by decreasing the duration of RNA polymerase II pausing in the promoter-proximal region, but how this is achieved remains unclear. Here we use a ‘multi-omics’ approach to demonstrate that the duration of polymerase pausing generally limits the productive frequency of transcription initiation in human cells (‘pause-initiation limit’). We further engineer a human cell line to allow for specific and rapid inhibition of the P-TEFb kinase CDK9, which is implicated in polymerase pause release. CDK9 activity decreases the pause duration but also increases the productive initiation frequency. This shows that CDK9 stimulates release of paused polymerase and activates transcription by increasing the number of transcribing polymerases and thus the amount of mRNA synthesized per time. CDK9 activity is also associated with long-range chromatin interactions, suggesting that enhancers can influence the pause-initiation limit to regulate transcription. eLife Sciences Publications, Ltd 2017-10-10 /pmc/articles/PMC5669633/ /pubmed/28994650 http://dx.doi.org/10.7554/eLife.29736 Text en © 2017, Gressel et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Gressel, Saskia Schwalb, Björn Decker, Tim Michael Qin, Weihua Leonhardt, Heinrich Eick, Dirk Cramer, Patrick CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title | CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title_full | CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title_fullStr | CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title_full_unstemmed | CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title_short | CDK9-dependent RNA polymerase II pausing controls transcription initiation |
title_sort | cdk9-dependent rna polymerase ii pausing controls transcription initiation |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669633/ https://www.ncbi.nlm.nih.gov/pubmed/28994650 http://dx.doi.org/10.7554/eLife.29736 |
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