Dynamic accessible regions and PML-RARα binding. (A) Enrichment of the accessible regions over the PML-RARα binding sites before (blue) and after (green) ATRA treatment. The plot represents the number of accessible regions enriched over a distance of ± 10 kb starting from the middle of the PML-RARα binding sites. (B) Overview of the LMO2 gene region in proliferating (blue) and ATRA-treated (green) NB4 cells. The depicted region shows an increase in accessibility on ATRA treatment. (C) Overview of the RUNX1 gene region in proliferating (blue) and ATRA treated (green) NB4 cells. The depicted region shows a decrease in accessibility on ATRA treatment. (D) Genomic annotation of ∼ 2300 and 2900 sites that display dynamic accessibility, respectively, gaining signal in proliferating and in ATRA-differentiated NB4 cells. Accessible sites were sorted in promoter (−500 bp up to 100 bp downstream of transcription start site), gene body (intron and exon), or intergenic (everything else) regions. Analysis was performed using the “Genomatix” tool for annotation and statistics. (E) Overview of NA-seq (Nlalll + Hpall) data at the PML-RARα targets RARβ and SPI1 showing accessibility changes on ATRA treatment. PML ChIP-seq indicating PML-RARα binding sites is plotted in red. NA-seq data in untreated cells are plotted in blue, whereas NA-seq data for ATRA treated cells are plotted in green. (F) DR motif analysis for PML-RARα binding sites, which show gain of accessibility after ATRA treatment (NB4 + ATRA), and for PML-RARα binding sites that lose accessibility (NB4 − ATRA).