Epigenetics Chromatin. 2026 Jun 10. doi: 10.1186/s13072-026-00681-2. Online ahead of print.
ABSTRACT
Cardiomyopathies constitute a heterogeneous group of myocardial disorders representing leading causes of heart failure and cardiovascular mortality worldwide. While genetic mutations have been extensively characterized across different cardiomyopathy subtypes, the mechanistic links between genotype and phenotype remain incompletely understood. This review synthesizes current knowledge regarding chromatin remodeling complexes and their roles in cardiac gene regulation under physiological and pathological conditions. Moreover, disease-specific chromatin remodeling patterns were examined across dilated, hypertrophic, arrhythmogenic, and restrictive cardiomyopathies, highlighting both conserved mechanisms and subtype-specific alterations. Chromatin remodeling alterations contribute significantly to cardiomyopathy pathogenesis across multiple subtypes. The reversibility of epigenetic modifications presents therapeutic opportunities not available with genetic interventions. Selective HDAC inhibitors and EZH2 antagonists show promise in preclinical models, though clinical translation requires development of cardiac-specific delivery systems. CRISPR-based epigenetic editing technologies offer future potential for precise genomic locus-specific interventions to reverse pathological transcriptional programs. Chromatin remodeling complexes including SWI/SNF (BAF), NuRD, Polycomb, ISWI, CHD, and INO80 families- modulate disease expression, progression, and phenotypic variability through epigenetic modifications and ATP-dependent chromatin remodeling. Emerging evidence demonstrates that chromatin remodelers interact dynamically with DNA methylation machinery, histone-modifying enzymes, and cardiac transcription factors to orchestrate pathological gene expression programs. Understanding these epigenetic mechanisms offers unprecedented opportunities for developing novel therapeutic strategies targeting the chromatin regulatory apparatus, potentially reversing maladaptive transcriptional programs that drive disease progression.
PMID:42271426 | DOI:10.1186/s13072-026-00681-2