PML-RARα binding protects against DNA methylation. (A) Distribution of methylation levels in PML-RARα– and SUZ12-binding sites compared with background methylation. The plot shows the distribution of methylation differences between APL and control samples within PML-RARα–binding sites (left) or SUZ12-binding sites (right) compared with nonbinding sites. PML-RARα–binding sites exhibited lower methylation than nonbinding sites in APL, P < .001. SUZ12-binding sites exhibited higher methylation than nonbinding sites in APL, P < .001.(B) Fractions of differentially methylated binding sites. Of 556 analyzed PML-RARα–binding sites, 9 were differentially methylated, 6 of which were hypomethylated. For SUZ12, 2228 binding sites could be evaluated. Of these, 216 exhibited differential methylation, with 214 of these hypermethylated. (C) DNA Methylation at the bona fide PML-RARα target Gfi1. Single CpG-site resolution methylation data were visualized. Each small vertical bar represents one CpG dinucleotide. The color encodes the degree of raw methylation ranging from green (low methylation = 0) to red (high methylation = 1).The number of CpGs contained in the respective CpG-island is shown at the bottom. At the top smoothed methylation values for APL and controls are shown with the bottom lane representing the methylation difference between the 2 groups (APL minus controls). (D) Methylation in and around PML-RARα–binding sites in APL cells and those from healthy controls. The curves visualize methylation levels of APL samples and control samples in and around PML-RARα–binding sites together with the 25% and 75% quantiles (dashed lines). (E) Methylation in and around SUZ12-binding sites in APL cells and those from healthy controls. The curves visualize methylation levels of APL samples and control samples around SUZ12-binding sites together with the 25% and 75% quantiles (dashed lines).