Protein Methyltransferases as Targets for Personalized Cancer Therapeutics

A variety of molecular mechanisms work together to effect strict control of gene transcription in human cells. Paramount among these mechanisms is a collection of post-translational modifications of chromatin that facilitate conformational transitions between transcriptionally permissive and suppressive chromatin structures (Figure 1; refs. 1, 2). Each of these modifications is catalyzed by a specific set of enzymes (Figure 2). Not surprisingly, dysregulation of chromatin modification leads to pathologic alterations in gene transcription, hence to human disease. Among chromatin modifying enzymes, the protein methyltransferases (PMTs) stand out due to the large size of the class, and the disease association of many of these enzymes (3).