The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome
Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During th...
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Veröffentlicht in: | Science (American Association for the Advancement of Science) 2013-08, Vol.341 (6147), p.1237973-1237973 |
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creator | Engreitz, Jesse M Pandya-Jones, Amy McDonel, Patrick Shishkin, Alexander Sirokman, Klara Surka, Christine Kadri, Sabah Xing, Jeffrey Goren, Alon Lander, Eric S Plath, Kathrin Guttman, Mitchell |
description | Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations. |
doi_str_mv | 10.1126/science.1237973 |
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We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1237973</identifier><identifier>PMID: 23828888</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>United States: The American Association for the Advancement of Science</publisher><subject>Animals ; Cell Differentiation ; Cell Line ; Chromatin - chemistry ; Chromatin - metabolism ; Chromosomes ; Female ; Females ; Genes ; Genome ; Genomes ; Government regulations ; Inactivation ; Male ; Mice ; Models, Genetic ; Ribonucleic acids ; RNA, Long Noncoding - chemistry ; RNA, Long Noncoding - metabolism ; Three dimensional ; Transcription, Genetic ; X Chromosome - metabolism ; X Chromosome - ultrastructure ; X Chromosome Inactivation</subject><ispartof>Science (American Association for the Advancement of Science), 2013-08, Vol.341 (6147), p.1237973-1237973</ispartof><rights>Copyright © 2013, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c553t-eae990b4eff46b97b4d09df04d698986335a3ea03edcbb43467529c4af51af513</citedby><cites>FETCH-LOGICAL-c553t-eae990b4eff46b97b4d09df04d698986335a3ea03edcbb43467529c4af51af513</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2884,2885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23828888$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Engreitz, Jesse M</creatorcontrib><creatorcontrib>Pandya-Jones, Amy</creatorcontrib><creatorcontrib>McDonel, Patrick</creatorcontrib><creatorcontrib>Shishkin, Alexander</creatorcontrib><creatorcontrib>Sirokman, Klara</creatorcontrib><creatorcontrib>Surka, Christine</creatorcontrib><creatorcontrib>Kadri, Sabah</creatorcontrib><creatorcontrib>Xing, Jeffrey</creatorcontrib><creatorcontrib>Goren, Alon</creatorcontrib><creatorcontrib>Lander, Eric S</creatorcontrib><creatorcontrib>Plath, Kathrin</creatorcontrib><creatorcontrib>Guttman, Mitchell</creatorcontrib><title>The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.</description><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Cell Line</subject><subject>Chromatin - chemistry</subject><subject>Chromatin - metabolism</subject><subject>Chromosomes</subject><subject>Female</subject><subject>Females</subject><subject>Genes</subject><subject>Genome</subject><subject>Genomes</subject><subject>Government regulations</subject><subject>Inactivation</subject><subject>Male</subject><subject>Mice</subject><subject>Models, Genetic</subject><subject>Ribonucleic acids</subject><subject>RNA, Long Noncoding - chemistry</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Three dimensional</subject><subject>Transcription, Genetic</subject><subject>X Chromosome - metabolism</subject><subject>X Chromosome - ultrastructure</subject><subject>X Chromosome Inactivation</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNks9r1UAQxxdR7PPp2ZssePGSdjeT_XURSrEqlBakgrd1s5k0W5Lsczcp-t83sc9ivdiBZQ7zmS-zX76EvObskPNSHmUfcPR4yEtQRsETsuHMiMKUDJ6SDWMgC82UOCAvcr5mbJkZeE4OStClXmpDvl92SL-FPNF-9F_Ojyn-3PUxTJlOXUIsmjDgmEMcXU-vcIwDUpd8Fyb005yQTpHmXULXUOdTzOvaokd9l-IQ84K_JM9a12d8te9b8vX0w-XJp-Ls4uPnk-OzwgsBU4EOjWF1hW1bydqoumqYaVpWNdJooyWAcICOATa-riuopBKl8ZVrBV8fbMn7O93dXA8LhOOUXG93KQwu_bLRBftwMobOXsUbC0ppuehvybu9QIo_ZsyTHUL22PduxDhnyzXTTDCp-P9RIaUWAPAItCol42bFt-TtP-h1nNNi_EoB44pptZ55dEf9tjthe_9FzuyaCbvPhN1nYtl487cz9_yfEMAtjji0nQ</recordid><startdate>20130816</startdate><enddate>20130816</enddate><creator>Engreitz, Jesse M</creator><creator>Pandya-Jones, Amy</creator><creator>McDonel, Patrick</creator><creator>Shishkin, Alexander</creator><creator>Sirokman, Klara</creator><creator>Surka, Christine</creator><creator>Kadri, Sabah</creator><creator>Xing, Jeffrey</creator><creator>Goren, Alon</creator><creator>Lander, Eric S</creator><creator>Plath, Kathrin</creator><creator>Guttman, Mitchell</creator><general>The 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>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20130816</creationdate><title>The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome</title><author>Engreitz, Jesse M ; Pandya-Jones, Amy ; McDonel, Patrick ; Shishkin, Alexander ; Sirokman, Klara ; Surka, Christine ; Kadri, Sabah ; Xing, Jeffrey ; Goren, Alon ; Lander, Eric S ; Plath, Kathrin ; Guttman, Mitchell</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c553t-eae990b4eff46b97b4d09df04d698986335a3ea03edcbb43467529c4af51af513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Chromatin - 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subjects | Animals Cell Differentiation Cell Line Chromatin - chemistry Chromatin - metabolism Chromosomes Female Females Genes Genome Genomes Government regulations Inactivation Male Mice Models, Genetic Ribonucleic acids RNA, Long Noncoding - chemistry RNA, Long Noncoding - metabolism Three dimensional Transcription, Genetic X Chromosome - metabolism X Chromosome - ultrastructure X Chromosome Inactivation |
title | The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome |
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