HistonMethyltransferasen

Histone methyltransferases, sometimes referred to in German as HistonMethyltransferasen, are enzymes that catalyze the transfer of a methyl group from S-adenosyl-L-methionine to specific amino acids on histone proteins. Methylation occurs primarily on lysine or arginine residues within histone tails and can either activate or repress transcription by influencing chromatin structure and the binding of effector proteins. These enzymes help establish and maintain epigenetic states that shape development, cellular identity, and responses to signals.

Histone methyltransferases are broadly divided into lysine methyltransferases (KMTs) and arginine methyltransferases (PRMTs). KMTs include SET-domain–containing enzymes, such as the SET1/MLL family that methylates H3K4, SETDB1 and SUV39H1 that target H3K9, and EZH2 in the PRC2 complex that trimethylates H3K27. Non-SET enzymes like DOT1L methylate H3K79. PRMTs catalyze arginine methylation, with Type I enzymes producing asymmetric dimethylarginine and Type II producing symmetric dimethylarginine; common examples include PRMT1 and PRMT5.

Mechanistically, methyltransfer reactions use SAM as the methyl donor, with activity often guided by protein partners and chromatin recruitment. Methylation marks are dynamic through coordinated activity of demethylases; lysine demethylases (KDMs) are well characterized, while arginine-demethylation mechanisms are less clearly defined. The interplay of histone marks and their readers determines chromatin states and transcriptional outcomes.

Biological and clinical relevance includes regulation of development, differentiation, imprinting, and genome stability. Dysregulation of histone methylation is associated with cancer and neurodevelopmental disorders. Therapeutic inhibitors targeting HMTs are under development; EZH2 inhibitors (for example, tazemetostat) are approved for certain cancers, while DOT1L inhibitors have been explored in specific leukemias.