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Lineage-Specific Genome Architecture Links Enhancers and Non-coding Disease Variants to Target Gene Promoters.
Javierre, Biola M; Burren, Oliver S; Wilder, Steven P; Kreuzhuber, Roman; Hill, Steven M; Sewitz, Sven; Cairns, Jonathan; Wingett, Steven W; Várnai, Csilla; Thiecke, Michiel J; Burden, Frances; Farrow, Samantha; Cutler, Antony J; Rehnström, Karola; Downes, Kate; Grassi, Luigi; Kostadima, Myrto; Freire-Pritchett, Paula; Wang, Fan; Stunnenberg, Hendrik G; Todd, John A; Zerbino, Daniel R; Stegle, Oliver; Ouwehand, Willem H; Frontini, Mattia; Wallace, Chris; Spivakov, Mikhail; Fraser, Peter.
Afiliação
  • Javierre BM; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Burren OS; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
  • Wilder SP; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge CB10 1SD, UK.
  • Kreuzhuber R; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge CB10 1SD, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedi
  • Hill SM; MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
  • Sewitz S; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Cairns J; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Wingett SW; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Várnai C; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Thiecke MJ; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Burden F; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Farrow S; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Cutler AJ; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
  • Rehnström K; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Downes K; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Grassi L; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK.
  • Kostadima M; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge CB10 1SD, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedi
  • Freire-Pritchett P; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
  • Wang F; MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge CB2 0SR, UK.
  • Stunnenberg HG; Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Radboud University Nijmegen, Geert Grooteplein Zuid 30, 6525 GA Nijmegen, the Netherlands.
  • Todd JA; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.
  • Zerbino DR; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge CB10 1SD, UK.
  • Stegle O; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge CB10 1SD, UK.
  • Ouwehand WH; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; British Heart Foundation Centre of Excellence, Division of Cardiovascular Me
  • Frontini M; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; National Health Service Blood and Transplant, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; British Heart Foundation Centre of Excellence, Division of Cardiovascular Me
  • Wallace C; JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; MRC Biostatistics Unit, Cambridge Institute of Public Health, Cambridge Biome
  • Spivakov M; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address: mikhail.spivakov@babraham.ac.uk.
  • Fraser P; Nuclear Dynamics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK. Electronic address: peter.fraser@babraham.ac.uk.
Cell ; 167(5): 1369-1384.e19, 2016 11 17.
Article em En | MEDLINE | ID: mdl-27863249
Long-range interactions between regulatory elements and gene promoters play key roles in transcriptional regulation. The vast majority of interactions are uncharted, constituting a major missing link in understanding genome control. Here, we use promoter capture Hi-C to identify interacting regions of 31,253 promoters in 17 human primary hematopoietic cell types. We show that promoter interactions are highly cell type specific and enriched for links between active promoters and epigenetically marked enhancers. Promoter interactomes reflect lineage relationships of the hematopoietic tree, consistent with dynamic remodeling of nuclear architecture during differentiation. Interacting regions are enriched in genetic variants linked with altered expression of genes they contact, highlighting their functional role. We exploit this rich resource to connect non-coding disease variants to putative target promoters, prioritizing thousands of disease-candidate genes and implicating disease pathways. Our results demonstrate the power of primary cell promoter interactomes to reveal insights into genomic regulatory mechanisms underlying common diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Sanguíneas / Doença / Regiões Promotoras Genéticas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Sanguíneas / Doença / Regiões Promotoras Genéticas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cell Ano de publicação: 2016 Tipo de documento: Article