PML-RARα binding and histone modification changes. ChIPs were performed with zinc-induced U937-PML-RARα cells (Pr9) and U937-empty vecor cells (PMT) with the indicated antibodies. Amplified ChIPs were hybridized on promoter and CpG island microarrays. Bioinformatics analyses identified PML-RARα–bound sequences and the histone modifications in the 2 cell lines. (A,B) The heatmaps of the 372 target genes indicate the average ratio between Pr9 versus PMT of the different arrays performed for each antibody. All values are visualized using the log ratio of signals in U937-PML-RARα versus control cell line (averages of 2-4 independent experiments). Red indicates an enrichment and green a decrease for PML-RARα or HDAC binding or the respective histone modification. The genes were clustered using a self-organizing map algorithm (with a 2 × 2 grid). The heatmaps were computed with Mayday. (A) Heatmap of promoter loci (271 genomic PML-RARα targets). (B) Heatmap of CpG island loci (101 genomic PML-RARα targets). (C-E) Enrichment of PML-RARα binding was categorized as absent (no), weak (> 1.25), intermediate (> 1.75), and strong (> 2.25) enrichment. The box plots indicate the range of changes for the different histone modifications between the promoters in U937-PML-RARα expressing versus U937–empty vector cells. The boxes indicate the range of 50% of the data points, and the whiskers contain 75% of the observed data points. The medians are indicated as horizontal lines in the boxes. The changes for acetylation of histone H3 and trimethylation of lysine 9 are statistically significant (P < .01), whereas dimethylation of lysine 4 is not.