Fig. 6: Changes in distal cis-regulatory elements in HPCs with C/EBPα mutation.

A Profiles of the ATAC-seq signals within each 2000-bp window centered on each peak for Day14 CD34⁺CD45⁺ HPC-iPSC derived from Low-risk MDS (C22) and from high-risk MDS (C22.7) (N = 2 independent experiments). Peaks are shown in order of decreasing log2 fold-difference between Low and High-risk samples (see the “Methods” section). Positions of transcription factor binding motifs are plotted alongside. B Motif enrichment analysis (Homer de novo motifs) for peaks only present in low-risk HPCs compared to unchanged peaks. C Motif enrichment analysis (Homer de novo motifs) for peaks only present in high-risk HPCs compared to unchanged peaks. D Pie chart showing the percentage of peaks at promoters and distal regulatory elements from peaks present in high-risk MDS HPCs only (left) or in low-risk MDS HPCs (right). E ATAC-seq UCSC genome browser screenshot depicting accessible chromatin sites being differentially regulated between the low- and high-risk HPCs. Red squares show differential ATAC-seq peaks between both conditions. Y-axis is set at 70 RPKM. F Profiles of the ATAC-seq signals within each 2000-bp window centered on each peak for CD34+ sorted cells from MDS27 patient samples before and after disease progression. Peaks are shown in order of decreasing log2-fold-difference between Low and High-risk samples (see the “Methods” section). Positions of transcription factor binding motifs are plotted alongside. G Motif enrichment analysis (Homer de novo motifs) for peaks only present in low-risk CD34⁺ cells compared to unchanged peaks. H Motif enrichment analysis (Homer de novo motifs) for peaks only present in high-risk CD34⁺ cells compared to unchanged peaks.