Abstract

Significance Using high-throughput experiments, we determined the functional epigenomic landscape in pancreatic islet cells. Computational integration of these data along with similar data from the ENCODE project revealed the presence of large gene control elements across diverse cell types that we refer to as “stretch enhancers.” Stretch enhancers are cell type specific and are associated with increased expression of genes involved in cell-specific processes. We find that genetic variations associated with common disease are highly enriched in stretch enhancers; notably, stretch enhancers specific to pancreatic islets harbor variants linked to type 2 diabetes and related traits. We propose that stretch enhancers form as pluripotent cells differentiate into committed lineages, to program important cell-specific gene expression.