title: Integrator regulates transcriptional initiation and pause release following activation.
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.
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gardini
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: David
authors.initials: D
authors.lastname: Baillat
authors.affiliation: The Fels Institute, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cesaroni
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Deqing
authors.initials: D
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Marinis
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Wagner
authors.affiliation: 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.
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136, USA.|The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Ramin
authors.initials: R
authors.lastname: Shiekhattar
mesh_terms: D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D012319:RNA Polymerase II / Q000378:metabolism*; D061785:Transcription Initiation, Genetic; D015533:Transcriptional Activation
chemical_list: D004815:Epidermal Growth Factor; D012319:RNA Polymerase II