Fig. 3: Epigenetic and transcriptional maps of identified T2D candidates.
Differential DNA methylation and expression (q < 0.05) in islets from 25 T2D cases vs. 75 controls overlap with islet-specific markers of transcriptional regulation24, 26, open chromatin regions (OCRs)16, and differentially methylated regions (DMRs) identified by whole-genome bisulfite sequencing (WGBS) of human islets6. a FOXP1 has 30 differentially methylated sites and reduced expression in islets from T2D cases vs. controls. This region overlaps with markers of active enhancers (class I-III; EI-EIII) and promoters (P), OCRs, and five islet-specific transcription factors (TFs). WGBS previously found 10 DMRs in FOXP1 in islets from T2D cases vs. controls. b TBC1D4 shows increased DNA methylation and decreased expression in islets from T2D cases vs. controls. This gene further displays 20 markers of the islet regulome, eight T2D-associated DMRs, 17 OCRs, and several binding regions for islet-specific TFs. c The TSS of RHOT1 displays an OCR, marks of active promoter and binding sites for three islet-specific TFs. RHOT1 expression was reduced and an intronic site showed reduced DNA methylation in islets from T2D cases vs. controls. d CABLES1 has altered methylation of five sites and reduced expression in islets from T2D cases vs. controls. TSS and the upstream region are in an OCR and have chromatin marks of active enhancer and promoter, and the region has 11 binding sites for islet-specific TFs. Chromosomal positions are based on hg38. Data presented as mean ± SEM. *q < 0.05 for T2D cases (n = 25) vs. Controls (n = 75 for DNA methylation and 72 for gene expression), based on linear regressions adjusted for age, BMI, sex, days in culture, and islet purity. The p-values were corrected for multiple testing with FDR analysis. Source data are provided as a Source Data file.
