Figure 4

(a) Bar graph of overlapping classified promoters (C1 sites), inactive enhancers (C2 sites), active enhancers (C3 sites), CTCF bound sites (C4 sites) and other sites (C5) and islet ATAC-seq peaks generated in non-diabetic donors. White bars (Peaks) represent classified promoter regions generated by Pasquali et al.¹¹, black bars (Overlaps) represent ATAC-seq peaks that overlap with classified promoter regions. Based on chi-square tests there were significantly more ATAC-seq peaks than expected by chance overlapping with C1, C2, C3 and C4 (*p < 0.00001, q < 0.01) while significantly less than expected overlapping with C5 (#p < 0.00001, q < 0.01). (b) Bar graph of overlapping transcription factor binding sites and islet ATAC-seq peaks generated in non-diabetic donors. White bars (All sites) represent transcription factor binding sites classified by Pasquali et al.¹¹, while black bars (Overlaps) represent ATAC-seq peaks that overlap with transcription factor binding sites. The binding of all these transcription factors was enriched in islet ATAC-seq peaks with p < 0.001 (*q < 0.018). The classified promoters and transcription factor binding sites were generated by Pasquali et al.¹¹. (c) Enrichment of transcription factor recognition sequences in ATAC-seq peaks of non-diabetic donors based on HOMER¹⁷. (d) Islet ATAC-seq peaks are enriched close to high-expressed transcripts. Here, we identified non-expressed transcripts based on transcript per million <0.1 and then divided the expressed transcripts into three equally sized groups that we categorize into low-, medium- and high-expressed transcripts. Proportion of non-, low-, medium-, and high-expressed transcripts that are within 1500 bp of a peak summit. As seen, ATAC-seq peaks were annotated to the majority of high-expressed transcripts, while only a small proportion of non-expressed genes have open chromatin nearby. There was also a clear gradual increase in the proportion of genes with increasing expression level. All three groups of expressed genes were significantly enriched based on chi-square testing (q < 0.001). T2D represents type 2 diabetes and ND represents non-diabetic. Gray region represents genes >1500 bp away from an ATAC-seq peak and black regions represents genes ≤1500 bp away from an ATAC-seq peak.