Downloads provided by UsageCountsA map of open chromatin in human pancreatic islets
Copyright policy )NIH| Comprehensive Identification of Active Functional Elements in Human Chromatin ,
NIH| Targeted Genetic Analysis of T2D and Quantitative Traits ,
NIH| Targeted Genetic Analysis of T2D and Quantitative Traits
Kyle J. Gaulton; Takao Nammo; Lorenzo Pasquali; Jeremy M. Simon; Paul G. Giresi; Marie P. Fogarty; Tami M. Panhuis; +8 Authors
Kyle J. Gaulton; Takao Nammo; Lorenzo Pasquali; Jeremy M. Simon; Paul G. Giresi; Marie P. Fogarty; Tami M. Panhuis; Piotr Mieczkowski; SECCHI , ANTONIO; Domenico Bosco; Thierry Berney; Eduard Montanya; Karen L. Mohlke; Jason D. Lieb; Jorge Ferrer;
A map of open chromatin in human pancreatic islets
Tissue-specific transcriptional regulation is central to human disease1. To identify regulatory DNA active in human pancreatic islets, we profiled chromatin by FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements)2–4 coupled with high-throughput sequencing. We identified ~80,000 open chromatin sites. Comparison of islet FAIRE-seq to five non-islet cell lines revealed ~3,300 physically linked clusters of islet-selective open chromatin sites, which typically encompassed single genes exhibiting 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 (T2D)5, is located in islet-selective open chromatin. We show that rs7903146 heterozygotes exhibit allelic imbalance in islet FAIRE signal, 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 identification of regulatory variants important for disease.
Italy, Spain, United Kingdom, Switzerland, United States, Spain
Islets of Langerhans/ metabolism, ADN, VARIANTS, SUSCEPTIBILITY, Regulatory Sequences, Nucleic Acid, Medical and Health Sciences, Chromatin/genetics/isolation & purification/ metabolism, Models, TRANSCRIPTION FACTOR, Cells, Cultured, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, Genetics & Heredity, RISK, Cultured, Diabetis, Regulatory Sequences, Nucleic Acid/drug effects/ genetics, Diabetes, Chromosome Mapping, Chromatin Assembly and Disassembly/ genetics, Biological Sciences, Bioinformatics and computational biology, Chromatin, INSIGHTS, Binding Sites/drug effects, Diabetes Mellitus, Type 2/genetics, TCF Transcription Factors, Life Sciences & Biomedicine, Sequence Analysis, Transcription Factor 7-Like 2 Protein, Type 2, Cells, Agricultural biotechnology, Formaldehyde/pharmacology, Bioinformatics and Computational Biology, ORGANIZATION, Models, Biological, Article, 576, Islets of Langerhans, BETA-CELLS, Formaldehyde, REVEALS, Genetics, Diabetes Mellitus, 617, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Metabolic and endocrine, TCF Transcription Factors/genetics, Science & Technology, Binding Sites, Nucleic Acid, DNA, Sequence Analysis, DNA, Biological, Chromatin Assembly and Disassembly, Diabetes Mellitus, Type 2, Hela Cells, Digestive Diseases, K562 Cells, Regulatory Sequences, Developmental Biology, HeLa Cells
Islets of Langerhans/ metabolism, ADN, VARIANTS, SUSCEPTIBILITY, Regulatory Sequences, Nucleic Acid, Medical and Health Sciences, Chromatin/genetics/isolation & purification/ metabolism, Models, TRANSCRIPTION FACTOR, Cells, Cultured, GENE-EXPRESSION, Oligonucleotide Array Sequence Analysis, Genetics & Heredity, RISK, Cultured, Diabetis, Regulatory Sequences, Nucleic Acid/drug effects/ genetics, Diabetes, Chromosome Mapping, Chromatin Assembly and Disassembly/ genetics, Biological Sciences, Bioinformatics and computational biology, Chromatin, INSIGHTS, Binding Sites/drug effects, Diabetes Mellitus, Type 2/genetics, TCF Transcription Factors, Life Sciences & Biomedicine, Sequence Analysis, Transcription Factor 7-Like 2 Protein, Type 2, Cells, Agricultural biotechnology, Formaldehyde/pharmacology, Bioinformatics and Computational Biology, ORGANIZATION, Models, Biological, Article, 576, Islets of Langerhans, BETA-CELLS, Formaldehyde, REVEALS, Genetics, Diabetes Mellitus, 617, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Metabolic and endocrine, TCF Transcription Factors/genetics, Science & Technology, Binding Sites, Nucleic Acid, DNA, Sequence Analysis, DNA, Biological, Chromatin Assembly and Disassembly, Diabetes Mellitus, Type 2, Hela Cells, Digestive Diseases, K562 Cells, Regulatory Sequences, Developmental Biology, HeLa Cells
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These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Citations provided by BIP!popularityPopularity provided by BIP!
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
Influence provided by BIP!impulseImpulse provided by BIP!
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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