Integrator regulates transcriptional initiation and pause release following activation

Alessandro Gardini; David Baillat; Matteo Cesaroni; Deqing Hu; Jill M Marinis; Eric J Wagner; Mitchell A Lazar; Ali Shilatifard; Ramin Shiekhattar

doi:10.1016/j.molcel.2014.08.004

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Integrator regulates transcriptional initiation and pause release following activation

Journal article

Open access

Peer reviewed

Integrator regulates transcriptional initiation and pause release following activation

Alessandro Gardini, David Baillat, Matteo Cesaroni, Deqing Hu, Jill M Marinis, Eric J Wagner, Mitchell A Lazar, Ali Shilatifard and Ramin Shiekhattar

Molecular cell, Vol.56(1), pp.128-139

2014-10-02

DOI: https://doi.org/10.1016/j.molcel.2014.08.004

PMCID: PMC4292851

PMID: 25201415

Abstract

Epidermal Growth Factor - physiology

Humans

Transcriptional Activation

Epidermal Growth Factor - metabolism

HeLa Cells

RNA Polymerase II - metabolism

Transcription Initiation, Genetic

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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.54 Molecular & Cell Biology - Genetics; 1.54.100 DNA Methylation
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology
ESI research areas: Molecular Biology & Genetics

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Details

Title: Integrator regulates transcriptional initiation and pause release following activation
Creators: Alessandro Gardini - The Wistar Institute, Philadelphia, PA 19104, USA
David Baillat - Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA
Matteo Cesaroni - The Fels Institute, Temple University School of Medicine, Philadelphia, PA 19140, USA
Deqing Hu - Stowers Institute for Medical Research, Kansas City, MO 64110, USA
Jill M Marinis - 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
Eric J Wagner - Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA
Mitchell A Lazar - 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
Ali Shilatifard - Stowers Institute for Medical Research, Kansas City, MO 64110, USA
Ramin Shiekhattar - The Wistar Institute, Philadelphia, PA 19104, USA
Publication Details: Molecular cell, Vol.56(1), pp.128-139
Publisher: United States
Grant note: R01 DK49780 / NIDDK NIH HHS P30 DK019525 / NIDDK NIH HHS 1F32DK09883901 / NIDDK NIH HHS 5T32HL007954-13F32 / NHLBI NIH HHS R01 CA166274 / NCI NIH HHS R01 DK049780 / NIDDK NIH HHS R01 GM078455 / NIGMS NIH HHS T32 HL007954 / NHLBI NIH HHS R01 GM105754 / NIGMS NIH HHS R01 CA089455 / NCI NIH HHS P30 CA010815 / NCI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 25201415
PMCID: PMC4292851
Record Identifier: 991031559795202976