Chromatin Remodeling by the Histone Methyltransferase SETD2 Drives Cardiometabolic Heart Failure with Preserved Ejection Fraction. 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