The Malignant Brain Tumor (MBT) domain is a protein module found in Polycomb group (PcG) proteins and tumor suppressors of the l(3)mbt family that binds prevalently mono- and di-methylated lysines on histone H3 and H4 tails during posttranslational modifications. According to structural analysis and sequence homology studies, the MBT domain comprising of Tudor, plant Agenet, Chromo and PWWP domains is evolutionary related to the Royal family of chromatin binding domains. Two distinct structural motifs have been identified in individual MBT domains, including an N-terminal arm of 30 to 50 amino acids and a C-terminal β subunit core of 60 to 80 amino acids.