Histone demethylase assay

To measure the activity of LSD1, a luminol‐based assay was used.30 A total of 5 µL of eluate was diluted in LSD1 reaction buffer (50 mM Tris, pH 8.5, 50 mM KCl, 5 mM MgCl₂, 5 nmol luminol, 20 μg/ml horseradish peroxidase, 1% Triton X‐100), and 10 µM H3K4me2 (1–21 aa) peptide was added as the substrate (all from Sigma). DMSO and inhibitors were added as indicated. The total volume per reaction was 100 µL. The samples were measured in a white 96‐well plate (Corning, Corning, NY) using an EnSpire multimode plate reader at an emission wavelength of 428 nm. Three individual purifications (n = 3) were used for the assay, with three technical replicates for each.