完整後設資料紀錄
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dc.contributor.authorTsai, Ping-Hsingen_US
dc.contributor.authorChien, Yuehen_US
dc.contributor.authorWang, Mong-Lienen_US
dc.contributor.authorHsu, Chih-Hungen_US
dc.contributor.authorLaurent, Benoiten_US
dc.contributor.authorChou, Shih-Jieen_US
dc.contributor.authorChang, Wei-Chaoen_US
dc.contributor.authorChien, Chian-Shiuen_US
dc.contributor.authorLi, Hsin-Yangen_US
dc.contributor.authorLee, Hsin-Chenen_US
dc.contributor.authorHuo, Teh-Iaen_US
dc.contributor.authorHung, Jui-Hungen_US
dc.contributor.authorChen, Chung-Hsuanen_US
dc.contributor.authorChiou, Shih-Hwaen_US
dc.date.accessioned2019-12-13T01:12:16Z-
dc.date.available2019-12-13T01:12:16Z-
dc.date.issued2019-11-04en_US
dc.identifier.issn0305-1048en_US
dc.identifier.urihttp://dx.doi.org/10.1093/nar/gkz801en_US
dc.identifier.urihttp://hdl.handle.net/11536/153149-
dc.description.abstractPluripotency and cell fates can be modulated through the regulation of super-enhancers; however, the underlying mechanisms are unclear. Here, we showed a novel mechanism in which Ash2l directly binds to super-enhancers of several stemness genes to regulate pluripotency and self-renewal in pluripotent stem cells. Ash2l recruits Oct4/Sox2/Nanog (OSN) to form Ash2l/OSN complex at the super-enhancers of Jarid2, Nanog, Sox2 and Oct4, and further drives enhancer activation, upregulation of stemness genes, and maintains the pluripotent circuitry. Ash2l knockdown abrogates the OSN recruitment to all super-enhancers and further hinders the enhancer activation. In addition, CRISPRi/dCas9-mediated blocking of Ash2l-binding motifs at these super-enhancers also prevents OSN recruitment and enhancer activation, validating that Ash2l directly binds to super-enhancers and initiates the pluripotency network. Transfection of Ash2l with W118A mutation to disrupt Ash2l-Oct4 interaction fails to rescue Ash2l-driven enhancer activation and pluripotent gene upregulation in Ash2l-depleted pluripotent stem cells. Together, our data demonstrated Ash2l formed an enhancer-bound Ash2l/OSN complex that can drive enhancer activation, govern pluripotency network and stemness circuitry.en_US
dc.language.isoen_USen_US
dc.titleAsh2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency networken_US
dc.typeArticleen_US
dc.identifier.doi10.1093/nar/gkz801en_US
dc.identifier.journalNUCLEIC ACIDS RESEARCHen_US
dc.citation.volume47en_US
dc.citation.issue19en_US
dc.citation.spage10115en_US
dc.citation.epage10133en_US
dc.contributor.department交大名義發表zh_TW
dc.contributor.department資訊工程學系zh_TW
dc.contributor.departmentNational Chiao Tung Universityen_US
dc.contributor.departmentDepartment of Computer Scienceen_US
dc.identifier.wosnumberWOS:000496767900021en_US
dc.citation.woscount0en_US
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