JACC Basic to Translational Science· 2026Q1
Histone Demethylase KDM5A Is Activated and Pathogenic in a Mouse Model of LMNA-Cardiomyopathy
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- Q1SCImago
- 2026year
Short summary
The histone demethylase KDM5A is activated in a mouse model of LMNA-cardiomyopathy, leading to repression of genes critical for heart function and survival.
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Key points
- KDM5A is identified as a key epigenetic mediator of heart failure in a lamin A-deficient mouse model.
- Activated KDM5A leads to reduced H3K4 trimethylation at gene promoters and repression of cardiac/metabolic genes.
- Genetic deletion of KDM5A restored H3K4 trimethylation, reactivated cardiac programs, and improved cardiac function.
- Improved cardiac function and prolonged survival were observed in mice lacking KDM5A.
AI-generated from the title and abstract; the full text is not read.
Abstract
Heart failure is associated with widespread epigenetic remodeling in cardiomyocytes, but the chromatin regulators driving this process remain poorly defined. We identify the histone H3K4 demethylase KDM5A as a key epigenetic mediator of heart failure in a cardiomyocyte-specific lamin A-deficient mouse model. Disease-associated activation of KDM5A leads to redistribution of promoter histone H3 lysine 4 trimethylation and repression of genes regulating sarcomere structure and mitochondrial oxidative metabolism. Genetic deletion of Kdm5a restores histone H3 lysine 4 trimethylation enrichment, reactivates cardiac and metabolic transcriptional programs, improves cardiac function, and prolongs survival. These findings identify KDM5A-mediated chromatin remodeling as a previously unrecognized mechanism of heart failure and highlight KDM5A as a potential therapeutic target.
The authors' abstract, as published at the source. JACC Basic to Translational Science, 2026 · DOI ↗
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Field: Cardiology and Cardiovascular Medicine
Cardiology and Cardiovascular MedicineMedicine