Fig. 3

Fig. 3

a Percentage of predicted zebrafish pancreatic enhancer sequences aligned to the human genome. Sequences are grouped in different clusters: “Pancreas” that includes PsE and DevE; “PsE”; “DevE”; “Embryo” that include putative enhancers active only during embryonic development. b PhastCons scores (99 vertebrate genomes against hg38) for human sequences converted from zebrafish putative enhancers. Grey dots label conserved sequences that do not overlap with H3K27ac mark in human pancreas (Pancreas-1801, PsE-1017, DevE-784 and Embryo-6792). Blue dots label conserved sequences that also show H3K27ac signal in human pancreas (ENCODE data; Pancreas-227, PsE-112, DevE-115). Green diamonds: average (grey dots: 0.40, 0.42, 0.36, 0.39; blue dots: 0.36, 0.41, 0.34, respectively for Pancreas, PsE, DevE and Embryo). Red line: median (grey dots: 0.10, 0.17, 0.05, 0.08; blue dots: 0.06, 0.09, and 0.03, respectively for pancreas, PsE, DevE and Embryo). The Embryo dataset is composed by different developmental stages (Dome, 80% Epiboly, 24 hpf and 48 hpf). c Ratio between the number of human sequences conserved with the zebrafish putative active enhancers (Pancreas-3.21, PsE-2.79, DevE-3.76 or Embryo-1.76) overlapping H3K27ac signal in human pancreas (ENCODE data) over the average of a 10⁵ random shuffling of human sequences overlapping with H3K27ac signal in human pancreas (Supplementary Dataset 3q; empirical p-value < 1E−5). d Heatmap showing -log₁₀(p-values) from hypergeometric enrichment test for pancreatic disease association on the genes linked by HiChIP to each enhancer cluster. Represented values meet the criteria: q-value ≤ 0.05 and fold enrichment≥1.5. e Genomic landscape of the human INSR gene (top) and zebrafish arid1ab ortholog (bottom), showing H3K27ac signal and predicted super-enhancers (blue). f Relevant pancreas transcription factors whose binding motifs are enriched in zebrafish pancreas H3K27ac ChIP-seq data. g Venn diagram of the top 140 enriched TFBS motifs in H3K27ac positive sequences in three different datasets: zebrafish pancreas (ZP), human pancreas (HP) and dome+80%epiboly embryos (D80). Number of motifs shared between pairs of groups (arrows). p-values are described (p; hypergeometric enrichment test). The enrichment of the observed vs expected is represented (E). p-values ≤ 0.05 were considered significant. For a–d, g, source data provided in Source Data file.