Fig. 2

Oxygen sensing mechanisms. In presence of oxygen, HIF α is hydroxylated by prolyl hydroxylase (PHD) and FIH (factor inhibiting HIF), leading to rapid proteosomal degradation mediated by von Hippel–Lindau (VHL) protein and failure of recruiting transcriptional coactivators. The absence of oxygen leads to the stabilization and translocation of HIF-α to the nucleus where it heterodimerizes with HIF-1β to form the HIF–α/1β complex. Then, this complex recruits transcriptional coactivator and regulates target gene expression. Histone lysine demethylases (KDMs) can directly sense oxygen to control cell fate by regulating the chromatin structure in a HIF-independent manner. For example, KDM6A and KDM5A are inactivated during hypoxia, causing hypermethylation of H3K27 (KDM6A target) and H3K4 (KDM5A target)