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Mol Cell. 2014 Oct 2;56(1):128-139. doi: 10.1016/j.molcel.2014.08.004. Epub 2014 Sep 4.

Integrator regulates transcriptional initiation and pause release following activation.

Author information

1
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
2
The Wistar Institute, Philadelphia, PA 19104, USA.
3
Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
4
The Fels Institute, Temple University School of Medicine, Philadelphia, PA 19140, USA.
5
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
6
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
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Contributed equally

Abstract

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.

PMID:
25201415
PMCID:
PMC4292851
DOI:
10.1016/j.molcel.2014.08.004
[Indexed for MEDLINE]
Free PMC Article

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