Whereas mono-, di- and trimethylation states of lysines on histones typically 
have specific functions, no specific functions have been attributed so far to 
the different methylation states of histone H3 Lysine 79 (H3K79) generated by 
Dot1. Here we show that Dot1, in contrast to other known histone 
methyltransferases, introduces multiple methyl groups via a nonprocessive 
mechanism. The kinetic mechanism implies that the H3K79 methylation states 
cannot be generated independently, suggesting functional redundancy. Indeed, 
gene silencing in yeast, which is dependent on Dot1, relied on global H3K79 
methylation levels and not on one specific methylation state. Furthermore, our 
findings suggest that histone H2B ubiquitination affects H3K79 trimethylation by 
enhancing synthesis of all H3K79 methylation states. Our results suggest that 
multiple methylation of H3K79 leads to a binary code, which is expected to limit 
the possibilities for regulation by putative demethylases or binding proteins.