Fig. 4

EpiCHAOS reveals elevated levels of epigenetic heterogeneity at PRC2 targeted regions and promoters of developmental genes. A Ordered dot plot showing epiCHAOS scores (epiCHAOS) computed across region sets for each ENCODE chromatin factor binding site in hematopoietic stem cells, ordered by epiCHAOS scores. The top 20 region sets (cell type and binding site) are labeled. B Scatter plot comparing epiCHAOS scores (epiCHAOS) with DNA methylation variation at each transcription factor binding site as in A. PRC2 targets (binding sites for EZH2/SUZ12, red), CTCF targets (orange), and cohesin binding sites (binding sites for RAD21/SMC3, blue) are highlighted. X-axis represents the average of per-CpG methylation variances across 10 individuals at all CpGs overlapping with the respective region set. Values are scaled to a 0–1 range. C Heatmaps show examples of high-epiCHAOS (EZH2 binding sites) and low-epiCHAOS (FOS binding sites) regions in the peaks matrix of scATAC-seq data from HSCs. D Ordered dot plot showing epiCHAOS scores (epiCHAOS) computed across promoters for each gene ontology biological process in hematopoietic stem cells, ordered by epiCHAOS scores. E Bar plot comparing epiCHAOS ranks for the set of bivalent genes across different hematopoietic cell types. The higher the rank indicates that the selected gene set has higher epiCHAOS scores compared to other gene sets in that celltype. Ranks were -log(10) transformed for display. F Volcano plot illustrates differential heterogeneity between hematopoietic stem cells and monocytes. Differential heterogeneity was tested for each ENCODE TFBS (binding sites measured in K562 cells). For each TFBS, the -log10(p-value) obtained by permutation test is displayed on the y-axis, and the difference in epiCHAOS scores between the two cell types is displayed on the x-axis