English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

CDK9-dependent RNA polymerase II pausing controls transcription initiation.

MPS-Authors
/persons/resource/persons180393

Gressel,  S.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons173057

Schwalb,  B.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

/persons/resource/persons127020

Cramer,  P.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

2492758.pdf
(Publisher version), 5MB

Supplementary Material (public)
There is no public supplementary material available
Citation

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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002E-1963-B
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.