ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation
Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb f...
Gespeichert in:
| Veröffentlicht in: | Science advances 2020-04, Vol.6 (14), p.eaay4858-eaay4858 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | eaay4858 |
|---|---|
| container_issue | 14 |
| container_start_page | eaay4858 |
| container_title | Science advances |
| container_volume | 6 |
| creator | Guo, Chenghao Che, Zhuanzhuan Yue, Junjie Xie, Peng Hao, Shaohua Xie, Wei Luo, Zhuojuan Lin, Chengqi |
| description | Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release. |
| doi_str_mv | 10.1126/sciadv.aay4858 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7112754</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2388004722</sourcerecordid><originalsourceid>FETCH-LOGICAL-c456t-d2885f47c40a8cb4cb15f99e11741c89a2bfbb2fe5510a210e5f60135b1a09a3</originalsourceid><addsrcrecordid>eNpVUcFuGyEURFWr2kp9zbHi6B7sAAu77KVSZblNJCs5xHf0FrM2FQtbYK3k1k_vWnat5PR4w7yZB4PQLSVLSll5l7SF3XEJ8MqlkB_QlBWVWDDB5cc35wmapfSbEEJ5WQpaf0aTgrGKkKKcor_rxw223mYL2STcDS7bIzjjM-4PkAxOpocI2QaPQ4vzYUSG3kRsXPD7M65D1zvzgufP69W3UWwEfI7BOev3OEJvdzhH8ElH258GwGHQJ5tT8wV9asElM7vUG7T9ud6u7hebp18Pqx-bheaizIsdk1K0vNKcgNQN1w0VbV0bSitOtayBNW3TsNYIQQkwSoxoS0IL0VAgNRQ36PtZth-azuz0-MAITvXRdhBfVQCr3t94e1D7cFTV-NOV4KPA_CIQw5_BpKw6m7RxDrwJQ1KskJIQXjE2Updnqo4hpWjaqw0l6hScOgenLsGNA1_fLnel_4-p-AeY1ZoZ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2388004722</pqid></control><display><type>article</type><title>ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Guo, Chenghao ; Che, Zhuanzhuan ; Yue, Junjie ; Xie, Peng ; Hao, Shaohua ; Xie, Wei ; Luo, Zhuojuan ; Lin, Chengqi</creator><creatorcontrib>Guo, Chenghao ; Che, Zhuanzhuan ; Yue, Junjie ; Xie, Peng ; Hao, Shaohua ; Xie, Wei ; Luo, Zhuojuan ; Lin, Chengqi</creatorcontrib><description>Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.aay4858</identifier><identifier>PMID: 32270036</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Biochemistry ; Cyclin T - metabolism ; Gene Expression Regulation ; Humans ; Models, Biological ; Molecular Biology ; Multiprotein Complexes - metabolism ; Protein Binding ; Protein Transport ; RNA-Binding Proteins - metabolism ; SciAdv r-articles ; Transcription Factors - metabolism ; Transcriptional Activation ; Transcriptional Elongation Factors - metabolism</subject><ispartof>Science advances, 2020-04, Vol.6 (14), p.eaay4858-eaay4858</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</rights><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). 2020 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-d2885f47c40a8cb4cb15f99e11741c89a2bfbb2fe5510a210e5f60135b1a09a3</citedby><cites>FETCH-LOGICAL-c456t-d2885f47c40a8cb4cb15f99e11741c89a2bfbb2fe5510a210e5f60135b1a09a3</cites><orcidid>0000-0001-8991-5693 ; 0000-0002-2121-584X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112754/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112754/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32270036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Chenghao</creatorcontrib><creatorcontrib>Che, Zhuanzhuan</creatorcontrib><creatorcontrib>Yue, Junjie</creatorcontrib><creatorcontrib>Xie, Peng</creatorcontrib><creatorcontrib>Hao, Shaohua</creatorcontrib><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Luo, Zhuojuan</creatorcontrib><creatorcontrib>Lin, Chengqi</creatorcontrib><title>ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release.</description><subject>Biochemistry</subject><subject>Cyclin T - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Models, Biological</subject><subject>Molecular Biology</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Protein Binding</subject><subject>Protein Transport</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>SciAdv r-articles</subject><subject>Transcription Factors - metabolism</subject><subject>Transcriptional Activation</subject><subject>Transcriptional Elongation Factors - metabolism</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUcFuGyEURFWr2kp9zbHi6B7sAAu77KVSZblNJCs5xHf0FrM2FQtbYK3k1k_vWnat5PR4w7yZB4PQLSVLSll5l7SF3XEJ8MqlkB_QlBWVWDDB5cc35wmapfSbEEJ5WQpaf0aTgrGKkKKcor_rxw223mYL2STcDS7bIzjjM-4PkAxOpocI2QaPQ4vzYUSG3kRsXPD7M65D1zvzgufP69W3UWwEfI7BOev3OEJvdzhH8ElH258GwGHQJ5tT8wV9asElM7vUG7T9ud6u7hebp18Pqx-bheaizIsdk1K0vNKcgNQN1w0VbV0bSitOtayBNW3TsNYIQQkwSoxoS0IL0VAgNRQ36PtZth-azuz0-MAITvXRdhBfVQCr3t94e1D7cFTV-NOV4KPA_CIQw5_BpKw6m7RxDrwJQ1KskJIQXjE2Updnqo4hpWjaqw0l6hScOgenLsGNA1_fLnel_4-p-AeY1ZoZ</recordid><startdate>20200401</startdate><enddate>20200401</enddate><creator>Guo, Chenghao</creator><creator>Che, Zhuanzhuan</creator><creator>Yue, Junjie</creator><creator>Xie, Peng</creator><creator>Hao, Shaohua</creator><creator>Xie, Wei</creator><creator>Luo, Zhuojuan</creator><creator>Lin, Chengqi</creator><general>American Association for the Advancement of Science</general><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>5PM</scope><orcidid>https://orcid.org/0000-0001-8991-5693</orcidid><orcidid>https://orcid.org/0000-0002-2121-584X</orcidid></search><sort><creationdate>20200401</creationdate><title>ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation</title><author>Guo, Chenghao ; Che, Zhuanzhuan ; Yue, Junjie ; Xie, Peng ; Hao, Shaohua ; Xie, Wei ; Luo, Zhuojuan ; Lin, Chengqi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-d2885f47c40a8cb4cb15f99e11741c89a2bfbb2fe5510a210e5f60135b1a09a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biochemistry</topic><topic>Cyclin T - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Models, Biological</topic><topic>Molecular Biology</topic><topic>Multiprotein Complexes - metabolism</topic><topic>Protein Binding</topic><topic>Protein Transport</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>SciAdv r-articles</topic><topic>Transcription Factors - metabolism</topic><topic>Transcriptional Activation</topic><topic>Transcriptional Elongation Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Chenghao</creatorcontrib><creatorcontrib>Che, Zhuanzhuan</creatorcontrib><creatorcontrib>Yue, Junjie</creatorcontrib><creatorcontrib>Xie, Peng</creatorcontrib><creatorcontrib>Hao, Shaohua</creatorcontrib><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Luo, Zhuojuan</creatorcontrib><creatorcontrib>Lin, Chengqi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Chenghao</au><au>Che, Zhuanzhuan</au><au>Yue, Junjie</au><au>Xie, Peng</au><au>Hao, Shaohua</au><au>Xie, Wei</au><au>Luo, Zhuojuan</au><au>Lin, Chengqi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2020-04-01</date><risdate>2020</risdate><volume>6</volume><issue>14</issue><spage>eaay4858</spage><epage>eaay4858</epage><pages>eaay4858-eaay4858</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Release of paused RNA polymerase II (Pol II) requires incorporation of the positive transcription elongation factor b (P-TEFb) into the super elongation complex (SEC), thus resulting in rapid yet synchronous transcriptional activation. However, the mechanism underlying dynamic transition of P-TEFb from inactive to active state remains unclear. Here, we found that the SEC components are able to compartmentalize and concentrate P-TEFb via liquid-liquid phase separation from the soluble inactive HEXIM1 containing the P-TEFb complex. Specifically, ENL or its intrinsically disordered region is sufficient to initiate the liquid droplet formation of SEC. AFF4 functions together with ENL in fluidizing SEC droplets. SEC droplets are fast and dynamically formed upon serum exposure and required for rapid transcriptional induction. We also found that the fusion of ENL with MLL can boost SEC phase separation. In summary, our results suggest a critical role of multivalent phase separation of SEC in controlling transcriptional pause release.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>32270036</pmid><doi>10.1126/sciadv.aay4858</doi><orcidid>https://orcid.org/0000-0001-8991-5693</orcidid><orcidid>https://orcid.org/0000-0002-2121-584X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2375-2548 |
| ispartof | Science advances, 2020-04, Vol.6 (14), p.eaay4858-eaay4858 |
| issn | 2375-2548 2375-2548 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7112754 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Biochemistry Cyclin T - metabolism Gene Expression Regulation Humans Models, Biological Molecular Biology Multiprotein Complexes - metabolism Protein Binding Protein Transport RNA-Binding Proteins - metabolism SciAdv r-articles Transcription Factors - metabolism Transcriptional Activation Transcriptional Elongation Factors - metabolism |
| title | ENL initiates multivalent phase separation of the super elongation complex (SEC) in controlling rapid transcriptional activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T17%3A53%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=ENL%20initiates%20multivalent%20phase%20separation%20of%20the%20super%20elongation%20complex%20(SEC)%20in%20controlling%20rapid%20transcriptional%20activation&rft.jtitle=Science%20advances&rft.au=Guo,%20Chenghao&rft.date=2020-04-01&rft.volume=6&rft.issue=14&rft.spage=eaay4858&rft.epage=eaay4858&rft.pages=eaay4858-eaay4858&rft.issn=2375-2548&rft.eissn=2375-2548&rft_id=info:doi/10.1126/sciadv.aay4858&rft_dat=%3Cproquest_pubme%3E2388004722%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2388004722&rft_id=info:pmid/32270036&rfr_iscdi=true |