Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants.

ABSTRACT: Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify t

SUBMITTER: Pasquali L 

PROVIDER: S-EPMC3935450 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature