2. Academic Validation
  3. Histone modification landscape and the key significance of H3K27me3 in myocardial ischaemia/reperfusion injury

Histone modification landscape and the key significance of H3K27me3 in myocardial ischaemia/reperfusion injury

  • Sci China Life Sci. 2023 Feb 13. doi: 10.1007/s11427-022-2257-9.
Le Ni # 1 2,  Bowen Lin # 1 2,  Yanping Zhang # 2 3,  Lingjie Hu 1 2,  Jianghua Lin 1 2,  Fengmei Fu 2 4,  Meiting Shen 1 2,  Can Li 2 4,  Lei Chen 1 2,  Jian Yang 1 2 5,  Dan Shi 6 7,  Yi-Han Chen 8 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 2 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • 3 Department of Vascular and Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • 4 Jinzhou Medical University, Liaoning, 121000, China.
  • 5 Shanghai Frontiers Science Center of Nanocatalytic Medicine, Shanghai, 200092, China.
  • 6 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. [email protected].
  • 7 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. [email protected].
  • 8 Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. [email protected].
  • 9 Key Laboratory of Arrhythmias of the Ministry of Education of China, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China. [email protected].
  • 10 Shanghai Frontiers Science Center of Nanocatalytic Medicine, Shanghai, 200092, China. [email protected].
  • 11 Department of Pathology and Pathophysiology, Tongji University School of Medicine, Shanghai, 200092, China. [email protected].
  • 12 Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai, 200092, China. [email protected].
  • # Contributed equally.
PMID: 36808292 DOI: 10.1007/s11427-022-2257-9
Abstract

Histone modifications play crucial roles in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury. However, a genome-wide map of histone modifications and the underlying epigenetic signatures in myocardial I/R injury have not been established. Here, we integrated transcriptome and epigenome of histone modifications to characterize epigenetic signatures after I/R injury. Disease-specific histone mark alterations were mainly found in H3K27me3-, H3K27ac-, and H3K4me1-marked regions 24 and 48 h after I/R. Genes differentially modified by H3K27ac, H3K4me1 and H3K27me3 were involved in immune response, heart conduction or contraction, Cytoskeleton, and angiogenesis. H3K27me3 and its methyltransferase polycomb repressor complex 2 (PRC2) were upregulated in myocardial tissues after I/R. Upon selective inhibition of EZH2 (the catalytic core of PRC2), the mice manifest improved cardiac function, enhanced angiogenesis, and reduced fibrosis. Further investigations confirmed that EZH2 inhibition regulated H3K27me3 modification of multiple pro-angiogenic genes and ultimately enhanced angiogenic properties in vivo and in vitro. This study delineates a landscape of histone modifications in myocardial I/R injury, and identifies H3K27me3 as a key epigenetic modifier in I/R process. The inhibition of H3K27me3 and its methyltransferase might be a potential strategy for myocardial I/R injury intervention.

Keywords

EZH2; H3K27me3; angiogenesis; histone modification; myocardial ischemia/reperfusion.

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