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

Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrate... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 29 October 2013, Vol.110(44), pp.17921-6
Main Author: Parker, Stephen C J
Other Authors: Stitzel, Michael L , Taylor, D Leland , Orozco, Jose Miguel , Erdos, Michael R , Akiyama, Jennifer A , Van Bueren, Kelly Lammerts , Chines, Peter S , Narisu, Narisu , Black, Brian L , Visel, Axel , Pennacchio, Len A , Collins, Francis S
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; PMID: 24127591 Version:1 ; DOI: 10.1073/pnas.1317023110
Link: http://pubmed.gov/24127591
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recordid: medline24127591
title: Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants
format: Article
creator:
  • Parker, Stephen C J
  • Stitzel, Michael L
  • Taylor, D Leland
  • Orozco, Jose Miguel
  • Erdos, Michael R
  • Akiyama, Jennifer A
  • Van Bueren, Kelly Lammerts
  • Chines, Peter S
  • Narisu, Narisu
  • Black, Brian L
  • Visel, Axel
  • Pennacchio, Len A
  • Collins, Francis S
subjects:
  • Cell Differentiation -- Physiology
  • Chromatin -- Physiology
  • Diabetes Mellitus, Type 2 -- Physiopathology
  • Enhancer Elements, Genetic -- Genetics
  • Epigenomics -- Methods
  • Gene Expression Regulation -- Physiology
  • Insulin-Secreting Cells -- Metabolism
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 29 October 2013, Vol.110(44), pp.17921-6
description: Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥ 3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched...
language: eng
source:
identifier: E-ISSN: 1091-6490 ; PMID: 24127591 Version:1 ; DOI: 10.1073/pnas.1317023110
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleChromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants
creatorParker, Stephen C J ; Stitzel, Michael L ; Taylor, D Leland ; Orozco, Jose Miguel ; Erdos, Michael R ; Akiyama, Jennifer A ; Van Bueren, Kelly Lammerts ; Chines, Peter S ; Narisu, Narisu ; Black, Brian L ; Visel, Axel ; Pennacchio, Len A ; Collins, Francis S
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subjectCell Differentiation -- Physiology ; Chromatin -- Physiology ; Diabetes Mellitus, Type 2 -- Physiopathology ; Enhancer Elements, Genetic -- Genetics ; Epigenomics -- Methods ; Gene Expression Regulation -- Physiology ; Insulin-Secreting Cells -- Metabolism
descriptionChromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥ 3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched...
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titleChromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants
descriptionChromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥ 3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched...
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5Gene Expression Regulation -- Physiology
6Insulin-Secreting Cells -- Metabolism
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titleChromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants
authorParker, Stephen C J ; Stitzel, Michael L ; Taylor, D Leland ; Orozco, Jose Miguel ; Erdos, Michael R ; Akiyama, Jennifer A ; Van Bueren, Kelly Lammerts ; Chines, Peter S ; Narisu, Narisu ; Black, Brian L ; Visel, Axel ; Pennacchio, Len A ; Collins, Francis S
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abstractChromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those from nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥ 3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched...
doi10.1073/pnas.1317023110
pmid24127591
date2013-10-29