EPAS1 and cancer: However, a master regulator of gene expression in cancer cells under acidic conditions is HIF-2α, which acts through the activation of NAD+-dependent histone deacetylases (sirtuins) 1 and 6 (SIRT1/6), leading to the deacetylation of lysine residues in the HIF-2α regulatory amino-terminal transactivation domain (N-TAD) (85).