Histone methyltransferase that specifically trimethylates histone H3 to form H3K79me3. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histone. L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(79)-[histone H3] + 3 S-adenosyl-L-homocysteine Ubiquitination of histone H2B to form H2BK123ub1 is required for efficient DOT1 methyltransferase activity on histone H3. In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones. Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.