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  CDK9-dependent RNA polymerase II pausing controls transcription initiation.

Gressel, S., Schwalb, B., Decker, T. M., Qin, W., Leonhardt, H., Eick, D., et al. (2017). CDK9-dependent RNA polymerase II pausing controls transcription initiation. eLife, 6: e29736. doi:10.7554/eLife.29736.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-1963-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-248C-D
Genre: Journal Article

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 Creators:
Gressel, S.1, Author              
Schwalb, B.1, Author              
Decker, T. M., Author
Qin, W., Author
Leonhardt, H., Author
Eick, D., Author
Cramer, P.1, Author              
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2017-10-10
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.7554/eLife.29736
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Title: eLife
Source Genre: Journal
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Pages: 24 Volume / Issue: 6 Sequence Number: e29736 Start / End Page: - Identifier: -