The Molecular Basis of Histone Methylation

As an integrated part of the complex array of post-translational modifications on histone, methylation mainly occurs on histone lysine and arginine residues and plays pivotal roles in the regulation of chromatin organization and function. Histone methylation is catalyzed by different groups of methyltransferases while methylation marks on different residues as well as different methylation states on the same residue serve as docking sites to recruit a variety of binding proteins harboring specific recognition domains. These methyl-histone binding proteins further recruit additional chromatin modifiers and other proteins to transduce methylation signals into diverse functional outcomes. Here we summarize histone methyltransferases and discuss their specificities and regulations for different methylation reactions. We also discuss specific methyl-histone recognition by different families of binding proteins at multiple molecular layers. Given that the disruption of histone methylation and recognition has been associated with altered gene function in various diseases and human malignancy, understanding the regulation of histone methylation and recognition will also provide molecular basics for therapeutics.