The methylation of lysine residues on histone tails, a histone modification associated with gene activation and silencing, is carried out by proteins containing a conserved catalytic SET domain. The SET domain consists of two non-contiguous regions formed by N- and C-terminal ends of the primary sequence, each region contains three-to-four short ??????-strands, a short helix and several loops that connect these secondary structural elements. The C-terminal end forms a topologically unusual and highly conserved knot-like structure in which a strand threads through a loop region (PMID:12575990).