Figure 2

Schematic representation of hypoxia-induced epigenetic changes. Hypoxic conditions modulate SCs expression profile via several mechanisms, included epigenetic modifications. The induced upregulation of HIF-1α and HIF-2α, drives the activation of several target genes. Also stem-related genes, such as OCT-4, could be re-expressed. The chromatin configuration of their promoter region becomes accessible to transcription factors, also consequently to the upregulation of histone demethylases JMJD1A and JMJD2B, that catalyse the removal of repressive histone marks (H3K9me2/3). Histone tails are characterized by active histone modifications (light or dark blue squares), such as acetylated H3-H4 or H3K4me2/3, and DNA is unmethylated (white rounds) at the promoter CpG sites (black lines). Hypoxia also induced global repression of gene transcription, associated with the upregulation of chromatin modifier enzymes, such as histone deacetylases (HDACs) and demethylases (G9a), that drive the formation of histone repressive marks (red and purple rounds), such as deacetylated H3-H4, H3K9me2/3 or H3K27me3. DNA methylation global level increases consequently to the upregulation of DNA methyltransferases (DNMTs) and gene expression is silenced. MiRNAs additional control of transcription and translation contributes to generate a gene expression profile that allows to reactivated stem-related genes, increase protection from oxidative stress, reduce DNA damage, increase glycolysis and angiogenesis, with the final result of enhancing cell viability and their regenerative potential.