Effect of TF loss on LSD1 inhibitor-induced changes in chromatin accessibility. (A-B) Composite plots show normalized ATAC-seq signal at GSK-LSD1-induced sites in PU.1 WT (A) and PU.1 depletion (B). (C-D) Composite plots show normalized ATAC-seq signal at GSK-LSD1–induced sites in C/EBPα WT (C) and C/EBPα KO (D). (E) Scatterplot of log₂ fold changes in ATAC-seq signal of GSK-LSD1 treatment vs control for PU.1 WT (x axis) and PU.1 depletion (y axis). Red indicates sites that increase 1.5-fold in WT that fail to reach such levels in the PU.1-depleted setting. (F) Scatterplot of log₂ fold changes in ATAC-seq signal of GSK-LSD1 treatment vs control for C/EBPα WT (x axis) and C/EBPα KO (y axis). Red indicates sites that increase 1.5-fold in WT that fail to reach such levels in the C/EBPα KO setting. (G) Pie charts representing the quantification of sites in panels E-F that either maintain or lose the increase in accessibility upon treatment with GSK-LSD1 in the setting of TF depletion. (H) Genome browser track showing normalized ATAC-seq and ChIP-seq signal under treatment and control conditions, centered on a site that fails to become induced in the setting of either PU.1 depletion or C/EBPα KO. (I) Heat map of normalized H3K27ac signal in normal hematopoietic development at all GSK-LSD1–induced ATAC-seq peaks, showing the majority of sites are active in cells associated with myeloid differentiation (clustered by k means with k = 5). CMP, common myeloid progenitor; EryA, erythroblasts A; EryB, erythroblasts B; GN, granulocyte; HSC, hematopoietic stem cell; MEP, megakaryocyte/erythrocyte progenitor; MF, macrophage; Mono, monocyte.