Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants

Epigenomics 0301 basic medicine Chromatin Immunoprecipitation Enhancer Elements Mice, Transgenic NISC Comparative Sequencing Program Transgenic 576 Mice 03 medical and health sciences Genetic Insulin-Secreting Cells Medicine and Health Sciences Diabetes Mellitus Genetics 2.1 Biological and endogenous factors Animals Humans Aetiology Luciferases Metabolic and endocrine Gene Expression Profiling Diabetes Human Genome Life Sciences High-Throughput Nucleotide Sequencing Cell Differentiation Chromatin 3. Good health Enhancer Elements, Genetic Diabetes Mellitus, Type 2 Gene Expression Regulation National Institutes of Health Intramural Sequencing Center Comparative Sequencing Program Authors Type 2 NISC Comparative Sequencing Program Authors Biotechnology Genome-Wide Association Study
DOI: 10.1073/pnas.1317023110 Publication Date: 2013-10-14T20:21:48Z
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.
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