FIG. 7.

Model illustrating the function of Cps40 in the regulation of histone methyltransferase activity of Set1/COMPASS. (A) Cps40 and Cps60 (yellow diamond) induce a conformational change of Set1/SET domain, pulling back Tyr1052 (light-purple trapezoid) so that its histone methyltransferase active site, encompassing the substrate of methylated lysine, becomes more open, making it easier to accommodate trimethylated lysine. Me, methyl group; yellow circle with black lines, nucleosome. (B) In the Y1052F mutant Set1, mono- and dimethylation proceed similarly to the process in the wild type. However, F1052 (dark purple), lacking the hydroxyl group (small blue trapezoid in panel A) from the phenol ring side chain, allows enough space for the methyltransferase to trimethylate the H3 peptide without the aid of Cps40. This model is consistent with our previous observation that the loss of Cps60 and Cps40 results in the loss of H3K4 trimethylation (24). SAM, S-adenosylmethionine.