Differential contribution of BMI1 and EZH2 to BC reprogramming. (A) Circos plot displays genome-wide regions bound by BMI1 and EZH2 by ChIP-seq and BC-specific DNA methylation regions. Chromosome 12 is enlarged to illustrate individual tracks. Each track shows the regional accumulation of the respective signals. Of note, in the lowest 2 tracks (changes in BMI1/EZH2 binding), the weaker binding (light color) dominates. Bottom right shows the BMI1 and EZH2 ChIP-seq tracks at a gene locus on chromosome 1, illustrating the consistent binding at a hypermethylated site and weaker binding in BC. (B) ChIP-seq heat maps displaying binding densities of BMI1 and EZH2 at transcription start sites (TSS). TSS of all plots are arranged in the same order defined by BMI1 densities in CP. Data of 1 representative patient out of 3 patients with CP and 3 patients with BC, respectively, is shown. Plots of all samples can be found in supplemental Figure 8A. Averaged binding profiles are plotted on top. Average expression levels of respective genes are shown in red/yellow heat maps (16 patients with CP vs 15 patients with BC from Figure 2). (C) Top GO terms for BMI1- and EZH2-bound genes in CML. (D) Top GO terms for genes that are bound by BMI1 and differentially expressed (FDR < 0.05; Log₂FC > 0.58 or <−0.58) after treatment with BMI1 inhibitor (BMI1i) PTC209 of CD34⁺ BC cells. (E-F) Enrichment analysis of BMI1 and EZH2 binding sites, each based on 3 CP and 3 BC samples, for DNA hypermethylated (red, E) or hypomethylated (blue, F) loci (as defined by 28 patients with CP vs 30 patients with BC in Figure 3A). Fold-enrichment for overlap is shown on the y-axis; negative logarithmic P values for enrichment are shown on the x-axis.