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A map of open chromatin in human pancreatic islets

Mohlke, Karen L ; Lieb, Jason D ; Ferrer, Jorge ; Gaulton, Kyle J ; Nammo, Takao ; Pasquali, Lorenzo ; Simon, Jeremy M ; Giresi, Paul G ; Fogarty, Marie P ; Panhuis, Tami M ; Mieczkowski, Piotr ; Secchi, Antonio ; Bosco, Domenico ; Berney, Thierry ; Montanya, Eduard

Nature genetics, 2010-03, Vol.42 (3), p.255-259 [Periódico revisado por pares]

New York, NY: Nature Publishing Group

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Título:
A map of open chromatin in human pancreatic islets
Autor: Mohlke, Karen L ; Lieb, Jason D ; Ferrer, Jorge ; Gaulton, Kyle J ; Nammo, Takao ; Pasquali, Lorenzo ; Simon, Jeremy M ; Giresi, Paul G ; Fogarty, Marie P ; Panhuis, Tami M ; Mieczkowski, Piotr ; Secchi, Antonio ; Bosco, Domenico ; Berney, Thierry ; Montanya, Eduard
Assuntos: ADN ; Binding sites ; Binding Sites - drug effects ; Biological and medical sciences ; Cells, Cultured ; Chemical properties ; Chromatin ; Chromatin - genetics ; Chromatin - isolation & purification ; Chromatin - metabolism ; Chromatin Assembly and Disassembly - genetics ; Chromatin. Chromosome ; Chromosome Mapping ; Diabetes ; Diabetes Mellitus, Type 2 - genetics ; Diabetis ; DNA ; Formaldehyde - pharmacology ; Fundamental and applied biological sciences. Psychology ; Genes ; Genetic aspects ; Genetic Predisposition to Disease ; Genetics of eukaryotes. Biological and molecular evolution ; HeLa Cells ; Humans ; Islands of Langerhans ; Islets of Langerhans - metabolism ; K562 Cells ; Methods ; Models, Biological ; Molecular and cellular biology ; Molecular genetics ; Oligonucleotide Array Sequence Analysis ; Regulatory Sequences, Nucleic Acid - drug effects ; Regulatory Sequences, Nucleic Acid - genetics ; RNA polymerase ; Sequence Analysis, DNA ; TCF Transcription Factors - genetics ; Transcription Factor 7-Like 2 Protein
É parte de: Nature genetics, 2010-03, Vol.42 (3), p.255-259
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Authors contributed equally to this work
Descrição: 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 ∼80,000 open chromatin sites. Comparison of FAIRE-seq data from islets to that from five non-islet cell lines revealed ∼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.
Editor: New York, NY: Nature Publishing Group
Idioma: Inglês

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A map of open chromatin in human pancreatic islets

Mohlke, Karen L ; Lieb, Jason D ; Ferrer, Jorge ; Gaulton, Kyle J ; Nammo, Takao ; Pasquali, Lorenzo ; Simon, Jeremy M ; Giresi, Paul G ; Fogarty, Marie P ; Panhuis, Tami M ; Mieczkowski, Piotr ; Secchi, Antonio ; Bosco, Domenico ; Berney, Thierry ; Montanya, Eduard

New York, NY: Nature Publishing Group

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