Chromatin Remodeling by the Histone Methyltransferase SETD2 Drives Cardiometabolic Heart Failure with Preserved Ejection Fraction
Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is highly prevalent and associated with a poor outcome. Pathological gene expressions in heart failure are accompanied by changes in active histone marks without major alterations in DNA methylation. Histone 3 trimethylation at lysine 36 (H3k36me3) - a chromatin signature induced by the histone methyltransferase SETD2 – has shown a strong correlation with changes in gene expression in the human failing heart; yet its role in cardiac disease is poorly understood. The present study investigates the role of SETD2/ H3k36me3 in cHFpEF. Overall design: ChIP-seq of H3K27ac, H3K4me, H3K4me3 and H3k27ac in cardiomyocytes obtained from control and HFpEF were analyzed