Schematic representation of epigenetic regulation of a leukemogenic locus (LL) framed by histone H3. (a) Histone acetyltransferases (HAT; e.g. MYST3) and histone methyltransferases (HMT; e.g. MLL) can activate the locus. (b) Reciprocally, the locus is repressed by polycomb complex PRC2 (which comprised EED, EZH2 and SUZ12 proteins). ASXL1 would direct PRC2 to the locus. Loss-of-function mutations in PRC2 components or in ASXL1 remove PRC2 repression. DNMT3A is involved in the formation of 5-methylcytosines (5mC) from cytosines and interacts with HMTs as well as with PRC2 components. TET2 mediates hydroxylation of 5mC to 5hmC. To function, TET2 requires α-ketoglutarate (αKG), which is provided by IDH1/2 proteins. Aberrant methylation patterns are caused by mutation in TET2 or in IDH1/2, which produces 2-hydroxyglutarate instead of αKG.