In addition to changes in HIF-α protein stability, an additional level of oxygen control is mediated by another dioxygenase called factor inhibiting HIF (FIH). FIH mediates asparagine hydroxylation in the transactivation domain of HIF-α, a modification that prevents efficient recruitment of coactivators such as p300/CBP to HIF-α, thus limiting the transcriptional output of HIF . It has been shown that FIH is still functional at oxygen concentrations where PHDs are already inhibited . Furthermore, genetic studies have shown that FIH regulates 40% of HIF-dependent genes . However, FIH knockout mice develop normally, suggesting that FIH is not involved in controlling HIF-dependent transcription during developmental hypoxia .