ArticleThe Journal of clinical investigation2017
The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Highlighting cardiovascular manifestations of kleefstra syndrome: literature review and clinical insights.BMC cardiovascular disorders · 2025Pooled it
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- Unraveling the complexity of the histone code: implications for gene regulation and disease.Genome biology · 2026Review
- Transcriptional regulation in heart development, disease and regeneration: reassessing the fetal gene hypothesis.Nature reviews. Cardiology · 2026Review
- Methylation-centric epigenetic regulation in dilated cardiomyopathy: mechanisms, metabolic interplay, and translational potential.Frontiers in cardiovascular medicine · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- Location and aetiology are determinants of fibroblast activation and heterogeneity in the failing human heart.Genome medicine · 2025Article
- Anti-ageing interventions for the treatment of cardiovascular disease.Cardiovascular research · 2025Review
- Putative Epigenetic Regulator microRNAs (epi-miRNAs) and Their Predicted Targets in High-Fat Diet-Induced Cardiac Dysfunction: An In Silico Analysis in Obese Rats.International journal of molecular sciences · 2025Article
- A Latent Cardiomyocyte Regeneration Potential in Human Heart Disease.Circulation · 2025Article
- Isoprenaline Inhibits Histone Demethylase LSD1 to Induce Cardiac Hypertrophy.Cardiovascular toxicology · 2025Article
- The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.Journal of translational medicine · 2024Article
- miR-31-5p suppresses myocardial hypertrophy by targeting Nfatc2ip.Journal of cellular and molecular medicine · 2024Article
- Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure.Scientific reports · 2024Article
- Arrhythmias including atrial fibrillation and congenital heart disease in Kleefstra syndrome: a possible epigenetic link.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2023Article
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- Plasma metabolomics profiles in Black and White participants of the Adventist Health Study-2 cohort.BMC medicine · 2023Article
- Distinct functions of EHMT1 and EHMT2 in cancer chemotherapy and immunotherapy.bioRxiv : the preprint server for biology · 2023Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 5 countries.
Funding
Abstract
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes. This analysis revealed the pervasive loss of euchromatic H3K9me2 as a conserved feature of pathological hypertrophy that was associated with reexpression of fetal genes. In hypertrophy, H3K9me2 was reduced following a miR-217-mediated decrease in expression of the H3K9 dimethyltransferases EHMT1 and EHMT2 (EHMT1/2). miR-217-mediated, genetic, or pharmacological inactivation of EHMT1/2 was sufficient to promote pathological hypertrophy and fetal gene reexpression, while suppression of this pathway protected against pathological hypertrophy both in vitro and in mice. Thus, we have established a conserved mechanism involving a departure of the cardiomyocyte epigenome from its adult cellular identity to a reprogrammed state that is accompanied by reexpression of fetal genes and pathological hypertrophy. These results suggest that targeting miR-217 and EHMT1/2 to prevent H3K9 methylation loss is a viable therapeutic approach for the treatment of heart disease.
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