Integrator Regulates Transcriptional Initiation and Pause Release following Activation

In unicellular organisms, initiation is the rate-limiting step in transcription; in metazoan organisms, the transition from initiation to productive elongation is also important. Here, we show that the RNA polymerase II (RNAPII)-associated multiprotein complex, Integrator, plays a critical role in b...

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Bibliographic Details
Published in:Molecular cell 2014-10, Vol.56 (1), p.128-139
Main Authors: Gardini, Alessandro, Baillat, David, Cesaroni, Matteo, Hu, Deqing, Marinis, Jill M., Wagner, Eric J., Lazar, Mitchell A., Shilatifard, Ali, Shiekhattar, Ramin
Format: Article
Language:English
Subjects:
Epidermal Growth Factor - metabolism
Epidermal Growth Factor - physiology
HeLa Cells
Humans
Metazoa
RNA Polymerase II - metabolism
Transcription Initiation, Genetic
Transcriptional Activation
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Summary:In unicellular organisms, initiation is the rate-limiting step in transcription; in metazoan organisms, the transition from initiation to productive elongation is also important. Here, we show that the RNA polymerase II (RNAPII)-associated multiprotein complex, Integrator, plays a critical role in both initiation and the release of paused RNAPII at immediate early genes (IEGs) following transcriptional activation by epidermal growth factor (EGF) in human cells. Integrator is recruited to the IEGs in a signal-dependent manner and is required to engage and recruit the super elongation complex (SEC) to EGF-responsive genes to allow release of paused RNAPII and productive transcription elongation. [Display omitted] •Integrator is recruited to protein-coding genes•Loss of Integrator abrogates immediate early gene responsiveness to EGF•Integrator plays a role in transcription initiation and pause release•Integrator physically associates with the SEC complex Gardini et al. show that Integrator recruits the SEC complex to protein-coding genes, facilitating stimulus-dependent transcription activation and release of paused RNA polymerase for productive transcription elongation.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2014.08.004