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Title

A map of open chromatin in human pancreatic islets

Authors
Gaulton, Kyle J.
Nammo, Takao
Pasquali, Lorenzo
Simon, Jeremy M.
Giresi, Paul G.
Fogarty, Marie P.
Panhuis, Tami M.
Mieczkowski, Piotr
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Published in Nature Genetics. 2010, vol. 42, no. 3, p. 255-259
Abstract Tissue-specific transcriptional regulation is central to human disease. To identify regulatory DNA active in human pancreatic islets, we profiled chromatin by formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). We identified approximately 80,000 open chromatin sites. Comparison of FAIRE-seq data from islets to that from five non-islet cell lines revealed approximately 3,300 physically linked clusters of islet-selective open chromatin sites, which typically encompassed single genes that have islet-specific expression. We mapped sequence variants to open chromatin sites and found that rs7903146, a TCF7L2 intronic variant strongly associated with type 2 diabetes, is located in islet-selective open chromatin. We found that human islet samples heterozygous for rs7903146 showed allelic imbalance in islet FAIRE signals and that the variant alters enhancer activity, indicating that genetic variation at this locus acts in cis with local chromatin and regulatory changes. These findings illuminate the tissue-specific organization of cis-regulatory elements and show that FAIRE-seq can guide the identification of regulatory variants underlying disease susceptibility.
Keywords Binding Sites/drug effectsCells, CulturedChromatin/genetics/isolation & purification/ metabolismChromatin Assembly and Disassembly/ geneticsChromosome MappingDiabetes Mellitus, Type 2/geneticsFormaldehyde/pharmacologyGenetic Predisposition to DiseaseHela CellsHumansIslets of Langerhans/ metabolismK562 CellsModels, BiologicalOligonucleotide Array Sequence AnalysisRegulatory Sequences, Nucleic Acid/drug effects/ geneticsSequence Analysis, DNATCF Transcription Factors/geneticsTranscription Factor 7-Like 2 Protein
Identifiers
PMID: 20118932
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Structures
Research groups Chirurgie viscérale (104)
La transplantation d'îlots de Langerhans (623)
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GAULTON, Kyle J. et al. A map of open chromatin in human pancreatic islets. In: Nature Genetics, 2010, vol. 42, n° 3, p. 255-259. https://archive-ouverte.unige.ch/unige:20626

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Deposited on : 2012-05-22

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