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  The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction

Yang, G., Weng, X., Zhao, Y., Zhang, X., Hu, Y., Dai, X., et al. (2017). The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction. Nature Communications, 8, 14941. doi:10.1038/ncomms14941.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BFD3-B Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C260-3
Genre: Journal Article

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 Creators:
Yang, Guang1, Author
Weng, Xinyu1, Author
Zhao, Yuhao1, Author
Zhang, Xinjian1, Author
Hu, Yuanping1, Author
Dai, Xin1, Author
Liang, Peng1, Author
Wang, Peng1, Author
Ma, LeiLei1, Author
Sun, Xiaolei1, Author
Hou, Lei1, Author
Xu, Huihui1, Author
Fang, Mingming1, Author
Li, Yuehua1, Author
Jenuwein, Thomas2, Author              
Xu, Yong1, Author
Sun, Aijun1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              

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 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.

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Language(s): eng - English
 Dates: 2017-03-31
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1038/ncomms14941
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 8 Sequence Number: - Start / End Page: 14941 Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723