Fig. 7.

ISL1 modulates expression profiles of endocrine cells in the P9 pancreas. a Volcano plot shows differentially expressed genes (Padj < 0.05 (displayed as –log₁₀) and log₂ fold change − 1 and 0.585) identified by RNA sequencing in 100 FACS-sorted endocrine cells from the P9 pancreas of Isl1CKO (n = 6) in comparison to the control (n = 5). Complete list of genes in Supplementary Dataset 1d. b The most enriched Gene Ontology (GO) biological processes for downregulated and upregulated genes identified by RNA-seq. Complete list of genes for the GO terms in Supplementary Dataset 1e. c Heatmap of insulin secretion genes from the GO analysis shows expression levels for each sample. d Heatmap shows the top upregulated genes in P9 endocrine cells of Isl1CKO that were found enriched in E14.5 endocrine progenitors of Isl1CKO based on deconvolution analyses (Supplementary Dataset 1f). e Venn diagram representing the overlap of genes with differential expression (RNA-seq) and genes with H3K4me3 and/or H3K27me3 marks (CUT&Tag-seq) in their promoter regions (± 3 kb from the TSS) in control and Isl1CKO endocrine cells at P9. f Overlap between H3K4me3 and H3K27me3 modifications in the promoter regions of differentially expressed genes in control and Isl1CKO endocrine cells. g Heatmap shows the selection of differentially expressed genes identified by RNA-seq (average expression level per control and Isl1CKO) correlating to differences in H3K4me3 and H3K27me3 modification patterns at their promoter regions (± 3 kb from the TSS) between control and Isl1CKO pancreatic endocrine cells at P9. h Genome track view of representative gene loci showing H3K4me3 (green), H3K27me3 (magenta), and negative antibody control IgG (grey) normalized read peaks based on CUT&Tag-seq data. The presence of both marks at the promoter region, representing a poised state, is shown in control cells for Fev, Chga, Chgb, and Abat genes associated with endocrine progenitors. In contrast, a poised state is shown at promoter regions of genes Pyy (α cells); Celsr1, and Glp1r (markers of ß cells) in Isl1CKO but not control cells. A silencing H3K27me3 mark is located at the promoter region of a key ß-cell maturation marker Ucn3 only in Isl1CKO cells