DOT1 Like, Histone H3 Methyltransferase (DOT1L)

DOT1L is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. DOT1L is a nucleosomal histone-3 (H3)-specific methyltransferase that requires the SAM and sequences between amino acids 351 and 472 for activity. Overexpression of DOT1L in human embryonic kidney cells significantly increased methylation of lys79 of H3, but had no effect on lys4 or lys9. Methylation of lys79, attributed to DOT1L, was regulated during the cell cycle in synchronized HeLa cells. The deduced 1,537-amino acid protein has a calculated molecular mass of 165 kD and contains a SAM (sterile alpha motif) domain for protein-protein interaction. DOT1L does not, however, have the SET domain found in most histone lysine methyltransferases.