Given that KDM2 enzymes require oxygen for their histone demethylase function, it would be tempting to speculate that, despite the increase in expression, their demethylase activity would still be low. However, their other protein domains would still be functional, and as such their role as ubiquitin ligases might be increased in hypoxia. However, currently very few targets are known for these proteins and, as such, further work directed at these questions is therefore need. It would thus be interesting to analyse which proteins KDM2 family members interact with and modify, and what the functional consequences are for the cell, when KDM2 levels increase or decrease. Given that the KDM2 family targets important histone methylation marks such histone H3 lysine 4 trimethylation (H3K4me3) and H3K36me/me2 , regulation of KDM2 abundance will impinge into the levels of these histone marks. This suggests that prolonged hypoxia could therefore change chromatin structure via the mechanism described here, where HIF-1 induces KDM2 protein changes. Analysis of histone marks in cells exposed to different periods of hypoxia would allow to determine how the action of KDM2 proteins is controlled under such stress conditions.