Histone Methyltransferases

Chromatin Regulation Team

Section: Section of Structural Biology

Post-translational modification of histone tails by methylation of lysine residues is a major factor in gene silencing phenomena. The SET domain family is the major group of enzymes responsible for this process. Originally identified through sequence homology and implicated in position effect variegation they were later identified as lysine methyltransferases.  Subsequently there has been an explosion of publications both on their function and the role of methylation of histone tails in various cellular phenomena including cancer.

Integral to the operation of the ‘histone code’ is the high specificity of the modifying enzymes. In the case of the methyltransferase enzymes this functions not only at the level of substrate recognition, ie, which lysine residue is modified, but also whether the lysine is mono-, di-, or tri- methylated. The latter adds a further level of complexity to the ‘histone code’ and understanding at the molecular level how this group of enzymes achieves their remarkable selectivity is an exciting area of ongoing research.