HMTase assay performed using 0.6 µM wild-type or mutant PRC2 complexes and either 1.29 µM H3 histone or 0.645 µM chromatinized DNA substrates, with the reaction buffer supplemented with KCl to a final concentration of 0, 50 and 100 mM. Three independent replicates were carried out on different days with similar results. Uncropped gel images used to generate this figure are in Supplementary Fig. 2 . Color key for all the schematic illustrations in this figure: PRC2 in gray, DNA in black, H3 histones in magenta and the other histones in pink.