Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury.
Y, L., Z, W., Y, Z., Y, M., J, Y., Y, S., Y, L., L, A., Z, P., & H, G. (2026). Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury.. Epigenetics. https://doi.org/10.1080/15592294.2026.2694817
Y L, Z W, Y Z, Y M, J Y, Y S, et al. Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury.. Epigenetics. 2026; doi: 10.1080/15592294.2026.2694817
Y L, Z W, Y Z, et al. Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury.[J]. Epigenetics. 2026. DOI: 10.1080/15592294.2026.2694817.
@article{y2026,
author = {Liu Y and Wang Z and Zhao Y and Ma Y and Yi J and Song Y and Liu Y and An L and Pan Z and Gao H},
title = {Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury.},
journal = {Epigenetics},
year = {2026},
doi = {10.1080/15592294.2026.2694817},
note = {PMID: 42384758},
}
TY - JOUR AU - Liu Y AU - Wang Z AU - Zhao Y AU - Ma Y AU - Yi J AU - Song Y AU - Liu Y AU - An L AU - Pan Z AU - Gao H TI - Dnmt1 associated Gja1 promoter methylation changes are implicated in Cx43 remodeling during acute myocardial ischemia/reperfusion injury. T2 - Epigenetics PY - 2026 DO - 10.1080/15592294.2026.2694817 AN - PMID:42384758 ER -
DNA methylation has traditionally been regarded as a stable epigenetic modification. However, emerging evidence indicates that oxidative and genotoxic stress can induce locus-specific methylation changes that modulate transcriptional responses. The contribution of such dynamic regulation to cardiac gene expression during myocardial ischemia/reperfusion injury (MIRI) remains incompletely understood. This study investigated whether altered methylation changes within the Gja1 promoter region are associated with connexin43 (Cx43) remodeling during MIRI. Male C57BL/6 mice were underwent global hypothermic I/R using a Langendorff-perfused heart model, with or without pretreatment using the DNA methyltransferase inhibitor 5-azacytidine (5-Aza, 3 μg/g body weight, i.p.). Gja1 promoter methylation was analyzed by BSP and MSP, while Dnmt1 enrichment was assessed by chromatin immunoprecipitation. Cx43 expression and localization were examined by qRT-PCR, Western blotting, and immunofluorescence, together with electrophysiological and histological analyses. MIRI was associated with Dnmt1 upregulation and nuclear enrichment, accompanied by altered methylation signals at selected CpG sites within the examined Gja1 promoter region and transcriptional repression. These changes coincided with reduced Cx43 expression, altered subcellular localization, impaired electrical conduction and increased arrhythmia susceptibility. Pretreatment with 5-Aza partially attenuated Gja1 promoter methylation signals and preserved Cx43 expression and localization during subsequent MIRI. These findings support an association between Dnmt1 enrichment, alteredGja1promoter CpG methylation, and Cx43 remodeling under reperfusion stress, suggesting that methylation-related epigenetic regulation may participate in Gja1 transcriptional responses during MIRI. Further temporal and gene-specific validation will be required to establish the kinetics and causal specificity of this pathway.