Extended Data Fig. 1: Chromatin characterization of human pancreatic β cells exposed to pro-inflammatory cytokines.

a, Pearson correlation values between replicates in different assays and conditions (see Supplementary Note 2). b, Volcano plots of ATAC-seq (left) and H3K27ac ChIP-seq (right) changes obtained after exposure of EndoC-βH1 to IFN-γ and IL-1β; green and red dots correspond to sites with absolute log₂ fold change > 1 and FDR adjusted P < 0.05 as calculated by fitting a negative binomial model in DESeq2. Chromatin changes are classified as ‘gained’ and ‘lost’ chromatin sites whereas non-significant changes are defined as ‘stable’. c, Chromatin accessibility and H3K27ac enrichment changes observed in EndoC-βH1 are largely replicated in human pancreatic islets as illustrated by the distribution of log₂ fold change at regions as classified in b in EndoC-βH1. Dotted lines indicate log₂ fold change thresholds (absolute log₂ fold change > 1). Box plot limits show upper and lower quartiles, whiskers extend to 1.5 times the interquartile range and the notch represents the confidence interval around the median. d, Hierarchical clustering using normalized ATAC-seq and H3K27ac read counts at EndoC-βH1 IREs shows that samples cluster according to treatment, suggesting that the differences caused by the proinflammatory cytokines are greater than those derived by the sample heterogeneity. HI = Human pancreatic islets, EndoC = EndoC-βH1 e, Distribution of distances to nearest TSS for the different types of regulatory elements, showing that IREs, compared with stable regulatory elements (SREs), are preferentially located distally to TSS. f, Mean sequence conservation score of IREs and a randomized set of IREs in placental mammals. Peaks were extended from the center 1 kb to each direction and mean score was calculated in 50 bp windows. g, Sequence composition analysis of IREs (n = 3,009) illustrating the top identified de novo motifs. 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).