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The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

Author

Listed:
  • Guang Yang

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Xinyu Weng

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University
    Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University
    Institute of Biomedical Sciences, Fudan University)

  • Yuhao Zhao

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Xinjian Zhang

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Yuanping Hu

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Xin Dai

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Peng Liang

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Peng Wang

    (Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University)

  • LeiLei Ma

    (Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University)

  • Xiaolei Sun

    (Institute of Biomedical Sciences, Fudan University)

  • Lei Hou

    (Institute of Biomedical Sciences, Fudan University)

  • Huihui Xu

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Mingming Fang

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University
    Jiangsu Jiankang Vocational College)

  • Yuehua Li

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Thomas Jenuwein

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Yong Xu

    (Key Laboratory of Cardiovascular Disease and Molecular Intervention and Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University)

  • Aijun Sun

    (Shanghai Institute of Cardiovascular Disease, Zhongshan Hospital, Fudan University
    Institute of Biomedical Sciences, Fudan University)

Abstract

Myocardial infarction (MI) dampens heart function and poses a great health risk. The class III deacetylase sirtuin 1 (SIRT1) is known to confer cardioprotection. SIRT1 expression is downregulated in the heart by a number of stress stimuli that collectively drive the pathogenesis of MI, although the underlying mechanism remains largely obscure. Here we show that in primary rat neonatal ventricular myocytes (NRVMs), ischaemic or oxidative stress leads to a rapid upregulation of SUV39H, the mammalian histone H3K9 methyltransferase, paralleling SIRT1 downregulation. Compared to wild-type littermates, SUV39H knockout mice are protected from MI. Likewise, suppression of SUV39H activity with chaetocin attenuates cardiac injury following MI. Mechanistically, SUV39H cooperates with heterochromatin protein 1 gamma (HP1γ) to catalyse H3K9 trimethylation on the SIRT1 promoter and represses SIRT1 transcription. SUV39H augments intracellular ROS levels in a SIRT1-dependent manner. Our data identify a previously unrecognized role for SUV39H linking SIRT1 trans-repression to myocardial infarction.

Suggested Citation

  • Guang Yang & Xinyu Weng & Yuhao Zhao & Xinjian Zhang & Yuanping Hu & Xin Dai & Peng Liang & Peng Wang & LeiLei Ma & Xiaolei Sun & Lei Hou & Huihui Xu & Mingming Fang & Yuehua Li & Thomas Jenuwein & Yo, 2017. "The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14941
    DOI: 10.1038/ncomms14941
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