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METTL3 regulates heterochromatin in mouse embryonic stem cells.
Xu, Wenqi; Li, Jiahui; He, Chenxi; Wen, Jing; Ma, Honghui; Rong, Bowen; Diao, Jianbo; Wang, Liyong; Wang, Jiahua; Wu, Feizhen; Tan, Li; Shi, Yujiang Geno; Shi, Yang; Shen, Hongjie.
Afiliação
  • Xu W; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Li J; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • He C; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Wen J; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Ma H; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • Rong B; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Diao J; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • Wang L; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Wang J; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • Wu F; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Tan L; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • Shi YG; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
  • Shi Y; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
  • Shen H; Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Nature ; 591(7849): 317-321, 2021 03.
Article em En | MEDLINE | ID: mdl-33505026
ABSTRACT
METTL3 (methyltransferase-like 3) mediates the N6-methyladenosine (m6A) methylation of mRNA, which affects the stability of mRNA and its translation into protein1. METTL3 also binds chromatin2-4, but the role of METTL3 and m6A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development5. METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m6A-methylated. These m6A-marked transcripts are bound by the m6A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m6A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Heterocromatina / Montagem e Desmontagem da Cromatina / Células-Tronco Embrionárias Murinas / Metiltransferases Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Heterocromatina / Montagem e Desmontagem da Cromatina / Células-Tronco Embrionárias Murinas / Metiltransferases Idioma: En Ano de publicação: 2021 Tipo de documento: Article