Supplementary Figure 5: H3K4me3 is reduced at regions that gain DNA methylation in patient fibroblasts.
a, Heatmaps of normalized H3K4me3 ChIP-seq reads in control (C1, C2) and patient (P1, P2) fibroblasts centered on DMRs with DNA methylation gain, ranked for DMR H3K4me3 levels in controls (C1, C2 mean). Scale indicates normalized read counts. Window size, 250 bp. b, Quantification of the data shown in a. Median H3K4me3 levels at hypermethylated DMRs (n = 1,129 DMRs). Median (dark) and 95% confidence intervals (light) for control (blue) and patient (red) dermal fibroblasts are plotted. Window size, 250 bp. H3K4me3 is significantly decreased at DMRs in patient samples (two-sided Wilcoxon rank-sum test, patients versus controls P=4.33 × 10–130, tested across the length of the DMR for normalized read counts). c, H3K4me3 is reduced in patients at Polycomb-marked DMVs. P value, two-sided Wilcoxon rank-sum test, Polycomb positive (+) (n = 524 DMVs) versus negative (–) DMVs (n = 628). d,e, Comparison of H3K4me3 at DMRs with other sites. d, Heatmaps for mean normalized H3K4me3 ChIP-seq reads in control (C1, C2 mean) and patient (P1, P2 mean) fibroblasts. Maps centered on reproducible H3K4me3 peaks that overlap Infinium DNA methylation probe sites. e, Quantification of the heatmap in d shows a significant decrease in H3K4me3 levels at hypermethylated DMRs compared to H3K4me3 peaks at other genomic locations. P value, two-sided Wilcoxon rank-sum test, hyper-DMRs (n = 720 H3K4me3 peaks) versus other sites (n = 14,850 H3K4me3 peaks) for log2 patients/controls). c,e, The y axes indicate the difference between patients and controls: 0, no change; >0, increased in patients; <0, decreased in patients. For the Polycomb-marked DMV definition, see Methods. Box, 25th–75th percentile; whiskers, 1.5× interquartile range.
