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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| Veröffentlicht in: | Molecular cell 2014-10, Vol.56 (1), p.128-139 |
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| container_title | Molecular cell |
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| creator | Gardini, Alessandro Baillat, David Cesaroni, Matteo Hu, Deqing Marinis, Jill M. Wagner, Eric J. Lazar, Mitchell A. Shilatifard, Ali Shiekhattar, Ramin |
| description | 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. |
| doi_str_mv | 10.1016/j.molcel.2014.08.004 |
| format | Article |
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[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.</description><identifier>ISSN: 1097-2765</identifier><identifier>EISSN: 1097-4164</identifier><identifier>DOI: 10.1016/j.molcel.2014.08.004</identifier><identifier>PMID: 25201415</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animalia ; DNA-directed RNA polymerase ; epidermal growth factor ; Epidermal Growth Factor - metabolism ; Epidermal Growth Factor - physiology ; genes ; HeLa Cells ; Humans ; Metazoa ; multiprotein complexes ; RNA Polymerase II - metabolism ; transcription (genetics) ; Transcription Initiation, Genetic ; Transcriptional Activation</subject><ispartof>Molecular cell, 2014-10, Vol.56 (1), p.128-139</ispartof><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><rights>2014 Elsevier Inc. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c665t-93d094fe94ecb79c9b5d026975be18d3e9c2c4d818cc977e1593a9266906fd6b3</citedby><cites>FETCH-LOGICAL-c665t-93d094fe94ecb79c9b5d026975be18d3e9c2c4d818cc977e1593a9266906fd6b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1097276514006376$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25201415$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gardini, Alessandro</creatorcontrib><creatorcontrib>Baillat, David</creatorcontrib><creatorcontrib>Cesaroni, Matteo</creatorcontrib><creatorcontrib>Hu, Deqing</creatorcontrib><creatorcontrib>Marinis, Jill M.</creatorcontrib><creatorcontrib>Wagner, Eric J.</creatorcontrib><creatorcontrib>Lazar, Mitchell A.</creatorcontrib><creatorcontrib>Shilatifard, Ali</creatorcontrib><creatorcontrib>Shiekhattar, Ramin</creatorcontrib><title>Integrator Regulates Transcriptional Initiation and Pause Release following Activation</title><title>Molecular cell</title><addtitle>Mol Cell</addtitle><description>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.</description><subject>Animalia</subject><subject>DNA-directed RNA polymerase</subject><subject>epidermal growth factor</subject><subject>Epidermal Growth Factor - metabolism</subject><subject>Epidermal Growth Factor - physiology</subject><subject>genes</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Metazoa</subject><subject>multiprotein complexes</subject><subject>RNA Polymerase II - metabolism</subject><subject>transcription (genetics)</subject><subject>Transcription Initiation, Genetic</subject><subject>Transcriptional Activation</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcGOFCEU7BiNu67-gTF99DIt0EDDxWSzUXeSTTRm9UpoeD0yYWAEeox_L70zrnpxTw9CVb2iqmleYtRhhPmbbbeL3oDvCMK0Q6JDiD5qzjGSw4piTh-fzmTg7Kx5lvMWVSAT8mlzRthCwuy8-boOBTZJl5jaz7CZvS6Q29ukQzbJ7YuLQft2HVxxerm0Otj2k54zVLgHXecUvY8_XNi0l6a4wx3sefNk0j7Di9O8aL68f3d7db26-fhhfXV5szKcs7KSvUWSTiApmHGQRo7MIsLlwEbAwvYgDTHUCiyMkcMAmMleS8K5RHyyfOwvmrdH3f087sAaCCVpr_bJ7XT6qaJ26t-X4L6pTTwoSiQRDFeB1yeBFL_PkIvauVxT9TpAnLMiqKYmBEHyQWjNnHBczaGHoUzwWqLoFwP0CDUp5pxgujePkVqKVlt1LFotnSkkVC260l79_fF70u9m_yQDNf6Dg6SycRAMWJfAFGWj-_-GX0pZvM0</recordid><startdate>20141002</startdate><enddate>20141002</enddate><creator>Gardini, Alessandro</creator><creator>Baillat, David</creator><creator>Cesaroni, Matteo</creator><creator>Hu, Deqing</creator><creator>Marinis, Jill M.</creator><creator>Wagner, Eric J.</creator><creator>Lazar, Mitchell A.</creator><creator>Shilatifard, Ali</creator><creator>Shiekhattar, Ramin</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TM</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20141002</creationdate><title>Integrator Regulates Transcriptional Initiation and Pause Release following Activation</title><author>Gardini, Alessandro ; 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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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>25201415</pmid><doi>10.1016/j.molcel.2014.08.004</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animalia DNA-directed RNA polymerase epidermal growth factor Epidermal Growth Factor - metabolism Epidermal Growth Factor - physiology genes HeLa Cells Humans Metazoa multiprotein complexes RNA Polymerase II - metabolism transcription (genetics) Transcription Initiation, Genetic Transcriptional Activation |
| title | Integrator Regulates Transcriptional Initiation and Pause Release following Activation |
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