Fig. 3: Progressive loss of DNAm at regulatory regions in beta cells with age (part II).
From: Epigenetic adaptation of beta cells across lifespan and disease
a, Enhancer methylation heatmap. Heatmap of average beta cell methylation at islet active enhancer regions32 (rows) across 21 HPAP CTL donors (columns), ordered by age, illustrating progressive demethylation with age. Methylation values are shown as fractions between 0 and 1. b, Linear fit slopes for enhancers. Violin plot of the slopes of linear fits to methylation versus age, corresponding to the regions in a. Mean slope = −0.0012; median slope = −0.0008. c,d, Pearson correlations for enhancers. Boxplot of Pearson correlation coefficients (c) and corresponding P values (d) for the 23,705 regions with negative methylation–age slopes from a. Boxplot parameters: middle line, median; box upper (resp. lower) bound, 3rd (resp. 1st) quartile; upper/lower whisker extends to the largest/smallest value within 1.5× the interquartile range (IQR); individual points, outliers. e, PDX1 binding sites methylation heatmaps. Heatmap of average beta cell methylation at PDX1 binding sites32, showing the 500 peaks with the greatest variability across CTL donors, ordered by age. Note the demethylation trend with age. f, Linear fit slopes for PDX1 binding sites. Violin plot of the slopes of linear fits to methylation versus age, corresponding to the regions in e. g,h, Pearson correlations for PDX1 binding sites. Boxplot of Pearson correlation coefficients (g) and corresponding P values (h) for the 447 regions with negative methylation–age slopes from e. Boxplot parameters: middle line, median; box upper (resp. lower) bound, 3rd (resp. 1st) quartile; upper/lower whisker extends to the largest/smallest value within 1.5× IQR; individual points, outliers. i, NKX6.1 binding sites methylation heatmaps. Heatmap of average beta cell methylation at NKX6.1 binding sites32, showing the 500 peaks with the greatest variability across CTL donors, ordered by age. Note the demethylation trend with age. j, Linear fit slopes for NKX6.1 binding sites. Violin plot of the slopes of linear fits to methylation versus age, corresponding to the regions in i. k,l, Pearson correlations for NKX6.1 binding sites. Boxplot of Pearson correlation coefficients (k) and corresponding P values (l) for the 448 regions with negative methylation versus age slopes from i. Boxplot parameters: middle line, median; box upper (resp. lower) bound, 3rd (resp. 1st) quartile; upper/lower whisker extends to the largest/smallest value within 1.5× IQR; individual points, outliers. m, Gene set enrichment results. Gene set enrichment for hypomethylated DMRs in beta cells, based on DMR-distal genes (FDR < 0.01 and |delta | >10%) from the CTL beta age comparison. The x axis displays −log10 of the unadjusted P values from a one-sided hypergeometric test.
