E-GEOD-23784 - Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci
Released on 2 November 2010, last updated on 1 May 2014
Identifying cis-regulatory elements is important to understand how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation marks (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ~18,000 putative promoters (several hundred novel and islet-active). Surprisingly, active promoter marks were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (non-promoter) regulatory elements, 47% are islet-unique and 22% are CTCF-bound. These findings present a global snapshot of the human islet epigenome and should provide functional context for non-coding variants emerging from genetic studies of T2D and other pancreatic islet disorders. Three different islet samples were tested for DNase I hypersensitivity by DNase-Seq. Five different primary pancreatic islet samples were evaluated for several chromatin modifications (H3K4me3, H3K4me1, H3K79me2) by ChIP-seq. One islet sample was evaluated for CTCF binding via ChIP-seq, All ChIP-seq samples have both non-specific IP (GFP) and input DNA controls.
Alan P Boyle, Daniel S Pearson, Elliott H Margulies, Francis S Collins, Gregory E Crawford, Laura J Scott, Lingyun Song, Michael Boehnke, Michael L Stitzel, Michael R Erdos, Peter S Chines, Praveen Sethupathy, Ryan Welch, Stephen C Parker, Terrence S Furey
Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L, Erdos MR, Welch R, Parker SC, Boyle AP, Scott LJ, NISC Comparative Sequencing Program, Margulies EH, Boehnke M, Furey TS, Crawford GE, Collins FS. , Europe PMC 21035756