Transcription factor enrichment analysis and ChIP sequencing of SUZ12 and REST in patient blasts. (A) Presence of published transcription factor binding sites among DMRs. The bars visualize the differences of observed and expected region centers in hypomethylated DMRs (green bars) and in hypermethylated DMRs (red bars). Two-sided binomial test: significance levels of 1 × 10-10 (***), 1 × 10-2 (**), or 5 × 10-2, respectively. (B) Methylation in SUZ12-binding sites. The density distribution of methylation levels in an APL patient sample within SUZ12 ChiP-Seq–binding sites is depicted. Methylation levels within ChiP-Seq data from the same APL patient and published binding sites from hESCs were analyzed. Solid lines indicate binding sites common to both hESCs and APL (shared sites); dashed lines, binding sites found only in APL (APL SUZ12 sites); dotted lines, binding sites found only in hESCs (hESC SUZ12 sites); and black solid line, genome-wide background methylation. Kolmogorov-Smirnov test: methylation in hESC SUZ12 > methylation in shared SUZ12 sites, P < .001. Methylation in shared SUZ12 sites > methylation in APL SUZ12 sites, P < .001. (C) Methylation in REST-binding sites. The density distribution of methylation levels in an APL patient sample within REST-binding sites is depicted. ChiP-Seq data from the same APL patient and published binding sites from hESCs were analyzed. Solid lines indicate binding sites common to both hESCs and APL cells (shared sites); dashed lines, binding sites found only in APL cells (APL REST sites); dotted lines, binding sites found only in hESCs (hESC REST sites); and black solid line, genome-wide methylation as a reference. Kolmogorov-Smirnov test: methylation in hESC REST > methylation in shared REST sites, P < .001. Methylation in shared REST sites > methylation in APL REST sites, P < .001.