Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes.

ABSTRACT: Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts in

SUBMITTER: Miguel-Escalada I 

PROVIDER: S-EPMC6640048 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature