Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos

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摘要N6-methyladenosine (m6A) on chromosome-associated regulatory RNAs (carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispens-able roles in the self-renewal and differentiation potency of mouse embryonic stem cells (ESCs),which highly depends on the m6A-binding ability.Ythdc1 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 scaffold.Detailed analyses revealed that YTHDC1 rec-ognizes m6A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdc1-depleted ESCs and inner cell mass (ICM) cells,which consequently increa-ses the transcriptional activities.Our study reveals a role of m6A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.

作者 Chuan Chen ^[1] Wenqiang Liu ^[2] Jiayin Guo ^[3] Yuanyuan Liu ^[3] Xuelian Liu ^[1] Jun Liu ^[4] Xiaoyang Dou ^[5] Rongrong Le ^[1] Yixin Huang ^[1] Chong Li ^[2] Lingyue Yang ^[2] Xiaochen Kou ^[1] Yanhong Zhao ^[1] You Wu ^[1] Jiayu Chen ^[2] Hong Wang ^[2] Bin Shen ^[3] Yawei Gao ^[1] Shaorong Gao ^[6] 学术成果认领

作者单位 Institute for Regenerative Medicine,Shanghai East Hospital,Shanghai Key Laboratory of Signaling and Disease Research,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200120,China ^[1] Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital,Shanghai Key Laboratory of Signaling and Disease Research,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China ^[2] State Key Laboratory of Reproductive Medicine,Department of Prenatal Diagnosis,Women's Hospital of Nanjing Medical University,Nanjing Maternity and Child Health Care Hospital,Nanjing Medical University,Nanjing 211166,China ^[3] School of Life Sciences,Peking University,Beijing 100871,China;Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China ^[4] Department of Chemistry and Institute for Biophysical Dynamics,The University of Chicago,Chicago,IL 60637,USA;Howard Hughes Medical Institute,Chicago,IL 60637,USA ^[5] Institute for Regenerative Medicine,Shanghai East Hospital,Shanghai Key Laboratory of Signaling and Disease Research,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200120,China;Clinical and Translation Research Center of Shanghai First Maternity & Infant Hospital,Shanghai Key Laboratory of Signaling and Disease Research,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China ^[6]

关键词 YTHDC1 LINE1-scaffold complex 2-cell retrotransposons H3K9me3

栏目名称 RESEARCH ARTICLES

发布时间 2021-07-19

基金项目

This work was supported by the National Key R&D Program of China the National Natural Science Foundation of China the Shanghai Rising-Star Program the Shanghai Municipal Medical and Health Dis-cipline Construction Projects the Fundamental Research Funds for the Central Universities and the Major Program of the Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone

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