DOT1L is capable of catalyzing the mono-, di-, and trimethylation of histone H3 in a nonprocessive manner (Min et al. 2003, Frederiks et al. 2008). It appear to be solely responsible for H3K79 methylation, since knockout of Dot1 in yeast, flies and mice results in complete loss of H3K79 methylation (van Leeuwen et al. 2002, Shanower et al. 2005, Jones et al. 2008).