nonSET: Dot1/KMT4 histone lysine methyltransferases do not contain a SET domain and methylate Lys-79 within the core domain of histone H3. In addition, Dot1/KMT4 methyltransferases only methylate nucleosomal substrates, not free histones. Structures of Dot1/KMT4 methyltransferases with AdoMet or AdoHcy bound reveal an extended AdoMet conformation that is in stark contrast to the folded U-shaped conformation found in SET domain methyltransferases. Sequence analysis suggests that Dot1/KMT4 methyltransferases possess AdoMet binding motifs similar to histone arginine methyltransferase family. (1)

Reference
1. Smith BC, Denu JM.Chemical mechanisms of histone lysine and arginine modifications. Biochimica Et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.2009;1789:45-57. PMID: 18603028.