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CDK9-dependent RNA polymerase II pausing controls transcription initiation.
eLife 6:e29736 (2017)
Publ. Version/Full Text
Postprint
Research data
DOI
PMC
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Computational Biology ; Human ; Systems Biology; Genome-wide; Elongation Complex; In-vivo; Pol Ii; Drosophila; Maps; Crispr-cas9; Inhibitors; Resolution; Promoters
ISSN (print) / ISBN
2050-084X
e-ISSN
2050-084X
Journal
eLife
Quellenangaben
Volume: 6,
Article Number: e29736
Publisher
eLife Sciences Publications
Publishing Place
Cambridge
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Functional Epigenetics (IFE)