Cracking the histone code: one, two, three methyls, you're out!

In this issue of Molecular Cell, Zhang et al. report the structure of a ternary complex between the SET domain histone methyltransferase DIM-5, its cofactor, and a histone H3 peptide. The insight gained from analysis of a key amino acid provides an exciting opportunity to dissect the possible functional meaning of mono-, di-, and trimethylation of histone lysine residues in vivo that will complement existing approaches in the quest to crack the histone methylation code.