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Gressel, S.* ; Schwalb, B.* ; Decker, T.-M. ; Qin, W.* ; Leonhardt, H.* ; Eick, D. ; Cramer, P.*

CDK9-dependent RNA polymerase II pausing controls transcription initiation.

eLife 6:e29736 (2017)
Publ. Version/Full Text Postprint Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
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, Issue: , Pages: , Article Number: e29736 Supplement: ,
Publisher eLife Sciences Publications
Publishing Place Cambridge
Reviewing status Peer reviewed