We have recently shown that the monomethylated lysine residues in DNMT1, E2F1, and SOX2 are recognized by L3MBTL3, a Malignant Brain Tumor (MBT) domain protein that specifically binds to methyl-lysine residues49, to target substrate proteolysis by the CRL4DCAF5 ubiquitin E3 ligase complex26,41. The gene discussed is SOX2; the disease is brain cancer.