Figure 3.

Chromatin oxygen sensing via JmjC histone demethylases and TETs. JmjC histone demethylases and TETs (mediators DNA demethylation) are 2-OGDs. Reduced activity of these enzymes in hypoxia, due to their oxygen sensitivity, can alter the chromatin landscape and mediate hypoxia induced transcription changes. Reduced activity of KDM5A in hypoxia increases H3K4me3 at the promoters of a subset hypoxia induced genes, facilitating their transcriptional activation. Reduced activity of KDM6A in hypoxia increases H3K27me3 at the promoters of a subset of hypoxia-repressed genes and represses their transcription. Reduced TET1/2 activity in hypoxia also represses gene transcription via DNA hypermethylation at gene promoters.