| Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. | |
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MedLine Citation:
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PMID: 21035756 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ∼18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders. |
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Authors:
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Michael L Stitzel; Praveen Sethupathy; Daniel S Pearson; Peter S Chines; Lingyun Song; Michael R Erdos; Ryan Welch; Stephen C J Parker; Alan P Boyle; Laura J Scott; ; Elliott H Margulies; Michael Boehnke; Terrence S Furey; Gregory E Crawford; Francis S Collins |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural |
Journal Detail:
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Title: Cell metabolism Volume: 12 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2011-03-10 Revised Date: 2011-11-03 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 443-55 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE23784 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Deoxyribonuclease I
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metabolism* Diabetes Mellitus, Type 2 / genetics* Epigenomics Genetic Loci Genome-Wide Association Study* Hela Cells Histones / genetics*, metabolism Humans Islets of Langerhans / metabolism* Lysine / metabolism Methylation Promoter Regions, Genetic Regulatory Sequences, Nucleic Acid Repressor Proteins / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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DK062370/DK/NIDDK NIH HHS; U54HG004563/HG/NHGRI NIH HHS; Z01-HG000024/HG/NHGRI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CCCTC-binding factor; 0/Histones; 0/Repressor Proteins; 56-87-1/Lysine; EC 3.1.21.1/Deoxyribonuclease I |
| Comments/Corrections | |
Erratum In:
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Cell Metab. 2010 Dec 1;12(6):683 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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