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
AUTHORS (48)
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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CITATIONS (627)
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