Hypoxia causes an increase in the level of HIF3A which in turn enhances expression of EPAS1 (HIF2A). The mechanism is unknown.
The EPAS1 (HIF2A) gene is transcribed to yield mRNA and the mRNA is translated to yield protein. EPAS1 is expressed in most adult tissues, but not in peripheral blood leukocytes (Tian et al. 1997). Normoxia causes constitutive oxygen-dependient hydroxylation of EPAS1 on asparagine and proline residues, resulting in degradation of EPAS1 via ubiquitinylation. Hypoxia therefore inhibits degradation of EPAS1 and also causes an increase in EPAS1 expression via HIF3A in embryonic stem cells, which experience hypoxic conditions in the reproductive tract prior to implantation (Forristal et al. 2010).