SET domain bifurcated 1 (SETDB1) and euchromatic histone lysine methyltransferase 2 (EHMT2) are H3K9 targeting histone methyltransferases (HMTs) that have been found to mediate gene repression in hypoxia via H3K9 methylation (Figure 2), with implications hypoxia-induced p53-dependent apoptosis and tumour growth, respectively [53,54]. The gene discussed is EHMT2; the disease is neoplasm.