Fig. 3

DNA methylation profiling in HGPS reveals two patient subgroups and lamina-associated domain (LAD)-enriched hypermethylation. a Scatter plot comparing the methylomes of HGPS and control fibroblasts. Differentially (P < 0.05, F-test) methylated probes are shown in blue. b Consensus clustering based on the 5000 most variable probe clusters between HGPS and control samples (1 = CpG islands, 2 = promoter, 3 = gene body, 4 = intergenic, 5 = lamin A-assoc., 6 = lamin B-assoc.). β values are colored from blue (β = 0) to red (β = 1). c Differential (β value) methylation of all (P < 2.20e−16), non-LAD- (P < 2.20e−16), lamin A LAD- (P < 2.20e−16), solo-WCGW HMD- (P = 4.42e−15), and solo-WCGW PMD- (P < 2.20e−16) associated probes (all: Welch’s two-sample t-test) with median indicated as a black line. HMD = highly methylated domain, PMD = partially methylated domain. d Enrichment of LAD-associated probes among all differentially (P < 0.05, F-test) methylated probes, as well as those hyper- and hypomethylated in HGPS samples (*P < 0.01, chi-squared test). Expected numbers were calculated based on the fraction of LAD-associated probes among all probes normalized to the number of differentially methylated probes. Sign = significantly. e Differential (β value) methylation of probes overlapping with different histone modifications. Median indicated as a black line. H3K4me1: P < 2.20e−16, H3K4me2: P < 2.20e−16, H3K4me3: P < 2.20e−16, H3K27ac: P < 2.20e−16, H3K36me3: P < 8.68e−15, H3K9me3: P < 2.20e−16, H3K27me3: P < 2.20e−16 (all: Welch’s two-sample t-test). Outliers were hidden for H3K4me3