Substrate methylation using 13C-SAM yields distinct peaks corresponding to mono-, di-, and tri-methyl-lysine. (A) Color-coded methylation scheme by a tri-methyltransferase enzyme. (B) 2D 1H, 13C-HSQC spectra showing methyl-lysine resonances at final experiment time points (red = Set7, blue = MLL1, and orange = PRMD9). (C) Sample time points of HSQC spectra showing the resonance intensities of the mono- and dimethyl peaks over time installed by MLL1. (D) Sample time points of PRDM9-installed mono-, di-, and trimethyl marks. To see this figure in color, go online.