Extended Data Fig. 3: Characterization of β-cell IREs.

a, Genes associated to different classes of IREs (classified as in Fig. 2a) show cytokine-induced expression in EndoC-βH1. CYT = cytokine exposed, CTRL = control. Boxplot limits show upper and lower quartiles, whiskers extend to 1.5 times the interquartile range and notch represents the median confidence interval. ***Wilcoxon test P < 0.001. b, Sequence conservation score of IREs and a corresponding randomized set used as control. c, Distribution of distances to nearest TSS of the different classes of open chromatin sites. Line indicates the threshold used to classify them as ‘promoters’. d, Number of IREs overlapping regions annotated as ‘Strong’ or ‘Weak’ enhancers by ENCODE ChromHMM. *Chi-squared P < 2 × 10⁻¹⁶. e, f, Top hits for de novo motif analysis in opening (e) and primed enhancers (f). Colors for matched genes correspond to RNA-seq (name) or protein (underlined) status (red = down-regulated, blue = equal-regulated, green = up-regulated, black/no-line = not-expressed/detected). g, Diagram showing the percentage of colocalization between the TF binding sites identified by de novo motif analysis in SRE and primed enhancers (that is excluding sites < 2Kb from a TSS). Label size indicates number of regions containing the TF binding sites and line width/intensity percentage of regions in which two motifs colocalize. h, Odds-ratio for finding a motif pair in the same enhancer in primed vs. SRE. Only significant pairs (FDR-adjusted Fisher’s Exact test P < 0.001) are shown. Immune and islet-specific TF motifs colocalize more often in primed compared to SRE chromatin sites. i, Percentage of overlap between EndoC-βH1 different classes of open chromatin and islet-specific TFs obtained by ChIP-seq in untreated human islets. j, Volcano plot showing differentially methylated sites (depicted in red) in EndoC-βH1 exposed or not to cytokines. Dotted lines indicate the threshold for methylation differences or significance using limma moderated t-test. k, Distribution of demethylated and stable CpGs according to different classes of open chromatin.