design: We extracted genomic DNA from left ventricle tissue following Qiagen DNeasys protocol (Qiagen). For RRBS, we digested high molecular weight genomic DNA with the Msp1 restriction enzyme. We prepared libraries following the NEBNext sample preparation kit protocol (New England Biolabs), with a spike-in of 1ng of enterobacteria phage DNA to each genomic library as a non-methylated internal control for estimating the efficiency of bisulfite (BS) conversion downstream.