Pancreatic progenitor epigenome maps prioritize type 2 diabetes risk genes with roles in development.

ABSTRACT: Genetic variants associated with type 2 diabetes (T2D) risk affect gene regulation in metabolically relevant tissues, such as pancreatic islets. Here, we investigated contributions of regulatory programs active during pancreatic development to T2D risk. Generation of chromatin maps from developmental precursors throughout pancreatic differentiation of human embryonic stem cells (hESCs) identifies enrichment of T2D variants in pancreatic progenitor-specific stretch enhancers that are not active in islets. Genes associated with progenitor-specific stretch enhancers are predicted to regulate developmental processes, most notably tissue morphogenesis. Through gene editing in hESCs, we demonstrate that progenitor-specific enhancers harboring T2D-associated variants regulate cell polarity genes

SUBMITTER: Geusz RJ 

PROVIDER: S-EPMC7864636 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature