| Adult mammalian cardiomyocytes exhibit limited proliferation. Our laboratory has identified cyclin A2 (CCNA2) as a critical driver of cardiomyocyte proliferation as well as a key repair factor following myocardial infarction (MI) in rodent and porcine models. CCNA2 is normally silenced early in the postnatal period, concomitant with cardiomyocyte cell cycle exit. Expression of a CCNA2 transgene is associated with reactivation of the endogenous CCNA2 gene. We hypothesize that epigenetic modifications regulate endogenous CCNA2 levels. We observed strikingly higher levels of H3K27me3 in wild-type adult (WT) mice in the CCNA2 gene compared to transgenic counterparts. H3K27me3 is understood to be an epigenetic mark indicative of gene silencing. An RNA-sequencing analysis of transgenic CCNA2 adult mouse cardiomyocytes compared to their WT counterparts revealed multiple downstream genes, including several previously uncharacterized, differentially expressed in these mice. These data will be utilized to generate novel therapies for regeneration of myocardium post-MI. |
