Cargando…
The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381011/ https://www.ncbi.nlm.nih.gov/pubmed/28361889 http://dx.doi.org/10.1038/ncomms14941 |
_version_ | 1782519851808456704 |
---|---|
author | Yang, Guang Weng, Xinyu Zhao, Yuhao Zhang, Xinjian Hu, Yuanping Dai, Xin Liang, Peng Wang, Peng Ma, LeiLei Sun, Xiaolei Hou, Lei Xu, Huihui Fang, Mingming Li, Yuehua Jenuwein, Thomas Xu, Yong Sun, Aijun |
author_facet | Yang, Guang Weng, Xinyu Zhao, Yuhao Zhang, Xinjian Hu, Yuanping Dai, Xin Liang, Peng Wang, Peng Ma, LeiLei Sun, Xiaolei Hou, Lei Xu, Huihui Fang, Mingming Li, Yuehua Jenuwein, Thomas Xu, Yong Sun, Aijun |
author_sort | Yang, Guang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5381011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53810112017-04-21 The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction Yang, Guang Weng, Xinyu Zhao, Yuhao Zhang, Xinjian Hu, Yuanping Dai, Xin Liang, Peng Wang, Peng Ma, LeiLei Sun, Xiaolei Hou, Lei Xu, Huihui Fang, Mingming Li, Yuehua Jenuwein, Thomas Xu, Yong Sun, Aijun Nat Commun Article 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. Nature Publishing Group 2017-03-31 /pmc/articles/PMC5381011/ /pubmed/28361889 http://dx.doi.org/10.1038/ncomms14941 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Yang, Guang Weng, Xinyu Zhao, Yuhao Zhang, Xinjian Hu, Yuanping Dai, Xin Liang, Peng Wang, Peng Ma, LeiLei Sun, Xiaolei Hou, Lei Xu, Huihui Fang, Mingming Li, Yuehua Jenuwein, Thomas Xu, Yong Sun, Aijun The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title | The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title_full | The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title_fullStr | The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title_full_unstemmed | The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title_short | The histone H3K9 methyltransferase SUV39H links SIRT1 repression to myocardial infarction |
title_sort | histone h3k9 methyltransferase suv39h links sirt1 repression to myocardial infarction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381011/ https://www.ncbi.nlm.nih.gov/pubmed/28361889 http://dx.doi.org/10.1038/ncomms14941 |
work_keys_str_mv | AT yangguang thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT wengxinyu thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT zhaoyuhao thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT zhangxinjian thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT huyuanping thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT daixin thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT liangpeng thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT wangpeng thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT maleilei thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT sunxiaolei thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT houlei thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT xuhuihui thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT fangmingming thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT liyuehua thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT jenuweinthomas thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT xuyong thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT sunaijun thehistoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT yangguang histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT wengxinyu histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT zhaoyuhao histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT zhangxinjian histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT huyuanping histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT daixin histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT liangpeng histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT wangpeng histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT maleilei histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT sunxiaolei histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT houlei histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT xuhuihui histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT fangmingming histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT liyuehua histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT jenuweinthomas histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT xuyong histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction AT sunaijun histoneh3k9methyltransferasesuv39hlinkssirt1repressiontomyocardialinfarction |