DNMT1 and heart failure: DNA methylation may also represent a cause of adult heart dysfunction in vertebrates as well, as upregulation of DNA methyltransferases 1 (DNMT1) and 3 (DNMT3) can upregulate (Wnt1/β-catenin signaling) or downregulate (pERK1/2 signaling) cellular pathways that promote cardiac fibrosis and heart failure with preserved ejection fraction [335] (Table 2 and Supplementary Table S7).