Nuclear m^(6)A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

作     者：Chuan Chen Wenqiang Liu Jiayin Guo Yuanyuan Liu Xuelian Liu Jun Liu Xiaoyang Dou Rongrong Le Yixin Huang Chong Li Lingyue Yang Xiaochen Kou Yanhong Zhao You Wu Jiayu Chen Hong Wang Bin Shen Yawei Gao Shaorong Gao Chuan Chen;Wenqiang Liu;Jiayin Guo;Yuanyuan Liu;Xuelian Liu;Jun Liu;Xiaoyang Dou;Rongrong Le;Yixin Huang;Chong Li;Lingyue Yang;Xiaochen Kou;Yanhong Zhao;You Wu;Jiayu Chen;Hong Wang;Bin Shen;Yawei Gao;Shaorong Gao

作者机构：Institute for Regenerative MedicineShanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Clinical and Translation Research Center of Shanghai First Maternity&Infant HospitalShanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Reproductive MedicineDepartment of Prenatal DiagnosisWomen's Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjing Medical UniversityNanjing 211166China School of Life SciencesPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Department of Chemistry and Institute for Biophysical DynamicsThe University of ChicagoChicagoIL 60637USA Howard Hughes Medical InstituteChicagoIL 60637USA 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2021年第12卷第6期

页      面：455-474页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100101[医学-人体解剖与组织胚胎学] 10[医学] 

基　　金：This work was supported by the National Key R&D Program of China(2016YFA0100400,2020YFA0113200,2018YFA0108900 and 2016YFC1000600) the National Natural Science Foundation of China(31922022,31771646,82022027,31721003,31970796,31871448 and 31871446) the Shanghai Rising-Star Program(19QA1409600) the Shanghai Municipal Medical and Health Discipline Construction Projects(2017ZZ02015) the Fundamental Research Funds for the Central Universities(1515219049 and 22120200410) the Major Program of the Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004) 

主　　题：YTHDC1 LINE1-scaffold complex 2-cell retrotransposons H3K9me3 

摘      要：N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains ***,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding *** is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 *** analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of ***,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional *** study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.