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FTO mediates LINE1 m6A demethylation and chromatin regulation in mESCs and mouse development.
Wei, Jiangbo; Yu, Xianbin; Yang, Lei; Liu, Xuelian; Gao, Boyang; Huang, Boxian; Dou, Xiaoyang; Liu, Jun; Zou, Zhongyu; Cui, Xiao-Long; Zhang, Li-Sheng; Zhao, Xingsen; Liu, Qinzhe; He, P Cody; Sepich-Poore, Caraline; Zhong, Nicole; Liu, Wenqiang; Li, Yanhe; Kou, Xiaochen; Zhao, Yanhong; Wu, You; Cheng, Xuejun; Chen, Chuan; An, Yiming; Dong, Xueyang; Wang, Huanyu; Shu, Qiang; Hao, Ziyang; Duan, Tao; He, Yu-Ying; Li, Xuekun; Gao, Shaorong; Gao, Yawei; He, Chuan.
Afiliação
  • Wei J; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Yu X; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Yang L; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Liu X; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Gao B; 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.
  • Huang B; 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.
  • Dou X; 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.
  • Liu J; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Zou Z; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Cui XL; State Key Laboratory of Reproductive Medicine, Suzhou Affiliated Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215002, China.
  • Zhang LS; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Zhao X; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Liu Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • He PC; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Sepich-Poore C; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Zhong N; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Liu W; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Li Y; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Kou X; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Zhao Y; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Wu Y; The Children's Hospital, School of Medicine, Zhejiang University, National Clinical Research Center for Child Health, Hangzhou 310052, China.
  • Cheng X; The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China.
  • Chen C; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • An Y; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Dong X; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Wang H; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Shu Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • Hao Z; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Duan T; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
  • He YY; Howard Hughes Medical Institute, The University of Chicago, Chicago, Chicago, IL 60637, USA.
  • Li X; 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.
  • Gao S; 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.
  • Gao Y; 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.
  • He C; 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.
Science ; 376(6596): 968-973, 2022 05 27.
Article em En | MEDLINE | ID: mdl-35511947
ABSTRACT
N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA. It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein FTO. Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates the transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oócitos / RNA Mensageiro / Cromatina / Adenosina / Regulação da Expressão Gênica no Desenvolvimento / Elementos Nucleotídeos Longos e Dispersos / Células-Tronco Embrionárias Murinas / Dioxigenase FTO Dependente de alfa-Cetoglutarato Limite: Animals Idioma: En Revista: Science Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oócitos / RNA Mensageiro / Cromatina / Adenosina / Regulação da Expressão Gênica no Desenvolvimento / Elementos Nucleotídeos Longos e Dispersos / Células-Tronco Embrionárias Murinas / Dioxigenase FTO Dependente de alfa-Cetoglutarato Limite: Animals Idioma: En Revista: Science Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos