A, Overview of the interaction between Dot1L, Ubiquitin and the nucleosome in the active state structure. Residues important for Dot1L interaction with the nucleosome acidic patch residues are depicted as red sticks. B, Detailed view of the contacts made between Dot1L and ubiquitin. Dot1L is depicted as a semi-transparent green cartoon. Important residues at the Dot1L-Ubiquitin interface are shown as sticks. C, Endpoint H3K79 methylation activity assays using Dot1L mutants with either unmodified or H2B-Ub nucleosomes. Error bars correspond to the standard deviation of 3 replicate experiments. D, Detailed view of interactions between Dot1L and the H2B/H2A acidic patch. Residues at the interface are depicted as sticks and the EM density for Dot1L in the active state is shown as a semi-transparent gray surface. A superimposed poised state Dot1L is depicted in yellow. E, Multiple Sequence alignment of Dot1L from different species. The alignment was performed with Clustal Omega (Sievers et al., 2011). See also Figures S3, S5 and Table S1.