Expression profiles of histone H4K20 methylation and its associated enzymes in mouse cardiac disease and human heart failure.

Histone H4K20 methylation is critical in regulating the cell cycle, DNA damage response, and gene repression in proliferating cells. However, its role in the heart remains poorly understood. Our previous work revealed that histone H4K20 tri-methylation is elevated in acute cell models of cardiomyocyte hypertrophy but is reduced in mouse models of cardiac hypertrophy and ischemia. Although these findings highlight the dynamic nature of this modification and its significance in regulating gene expression, the data on enzymes regulating H4K20 methylation is sparse. To build upon this work and investigate H4K20 di-methylation and the enzymes modulating this site in cardiac pathology, we quantified histone H4K20 di-methylation and 12 methyltransferases and demethylases across one cell model, two mouse models of cardiac dysfunction, and cardiac tissue from heart failure patients. While we observed no global changes in H4K20 di-methylation, we detected alterations in methyltransferases KMT5C and SMYD5 and demethylases RAD23A and KDM7C in humans and mice. These findings suggest changes in H4K20 di-methylation may occur on an individual gene basis but do not lead to global alterations in H4K20 di-methylation. Additionally, this work identified four enzymes differentially modulated in cardiac dysfunction to advance our understanding of epigenetic mechanisms involved in heart disease.

Duke Scholars

Author Christos Kyriakopoulos