完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Tsai, Ping-Hsing | en_US |
dc.contributor.author | Chien, Yueh | en_US |
dc.contributor.author | Wang, Mong-Lien | en_US |
dc.contributor.author | Hsu, Chih-Hung | en_US |
dc.contributor.author | Laurent, Benoit | en_US |
dc.contributor.author | Chou, Shih-Jie | en_US |
dc.contributor.author | Chang, Wei-Chao | en_US |
dc.contributor.author | Chien, Chian-Shiu | en_US |
dc.contributor.author | Li, Hsin-Yang | en_US |
dc.contributor.author | Lee, Hsin-Chen | en_US |
dc.contributor.author | Huo, Teh-Ia | en_US |
dc.contributor.author | Hung, Jui-Hung | en_US |
dc.contributor.author | Chen, Chung-Hsuan | en_US |
dc.contributor.author | Chiou, Shih-Hwa | en_US |
dc.date.accessioned | 2019-12-13T01:12:16Z | - |
dc.date.available | 2019-12-13T01:12:16Z | - |
dc.date.issued | 2019-11-04 | en_US |
dc.identifier.issn | 0305-1048 | en_US |
dc.identifier.uri | http://dx.doi.org/10.1093/nar/gkz801 | en_US |
dc.identifier.uri | http://hdl.handle.net/11536/153149 | - |
dc.description.abstract | Pluripotency 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.iso | en_US | en_US |
dc.title | Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1093/nar/gkz801 | en_US |
dc.identifier.journal | NUCLEIC ACIDS RESEARCH | en_US |
dc.citation.volume | 47 | en_US |
dc.citation.issue | 19 | en_US |
dc.citation.spage | 10115 | en_US |
dc.citation.epage | 10133 | en_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.department | National Chiao Tung University | en_US |
dc.contributor.department | Department of Computer Science | en_US |
dc.identifier.wosnumber | WOS:000496767900021 | en_US |
dc.citation.woscount | 0 | en_US |
顯示於類別: | 期刊論文 |