Epigenetic regulation of hypoxia-responsive gene expression: focusing on chromatin and DNA modifications

Mammalian cells constantly encounter hypoxia, which is a stress condition occurring during development and physiological processes. To adapt to this inevitable condition, cells develop various mechanisms to cope with this stress and survive. In addition to the activation/stabilization of transcriptional regulators (hypoxia-inducible factors), other epigenetic mechanisms of gene regulation are used. These mechanisms are mediated by various players including transcriptional coregulators, chromatin-modifying complexes, histone modification enzymes and changes in DNA methylation status. Recent progress in all the fields mentioned above has greatly improved the knowledge of how gene regulation contributes to the hypoxic response. This review should shed light on the molecular epigenetic mechanisms of hypoxia-induced gene regulation and help understand the processes adapted by cells to cope with hypoxia.