Novel Molecular Targets Participating in Myocardial Ischemia-Reperfusion Injury and Cardioprotection

Figure 2

Potential regulation of histone methylation/demethylation underlying MIRI. (a) MIRI can cause increased cardiac H3K9me3 at the proximal SIRT1 promoter through responsive SUV39H1, which may subsequently inhibit the transcription of SIRT1. (b) Increased H3K9me2 post-IP is G9a-dependent and potentially suppresses Mtor and other MIRI responsive genes. (c) KDM3A demethylates H3K9 at the NOX promoter and interacts with BRG1 in order to activate NOX transcription, the suppression of which is paralleled by the local reappearance of H3K9me2. (d, e) The LSD1-guided demethylation of the promoter H3K4me1/2 of Pld1 and Lpcat2 may be cardioprotective against MIRI. dsDNA, double-stranded deoxyribonucleic acid; H3K9me3, trimethylation of lysine 9 of histone 3; H3K9me2, bimethylation of lysine 9 of histone 3; H3K4me1, monomethylation of lysine 4 of histone 3; H3K4me2, bimethylation of lysine 4 of histone 3.