Fig. (2). Plausible mechanisms for hypoxia-induce down-regulation of cardioprotective genes in hearts.
Hypoxia causes the stabilization of HIF-1α and increased ROS production in fetal hearts. These events either act in collusion or independently to cause the recruitment of epigenetic modifiers, i.e. DNA methyltransferase (DNMT) or histone deacetylases (HDAC). These modifiers increase methylation of promoter at transcription factor binding sites and deacetylate histone residues resulting in the decreased transcription of cardioprotective genes (ex. PKCε, HSP70) and decreased cardioprotection in the long-term.