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Genetic determinants of co-accessible chromatin regions in activated T cells across humans.
Gate, Rachel E; Cheng, Christine S; Aiden, Aviva P; Siba, Atsede; Tabaka, Marcin; Lituiev, Dmytro; Machol, Ido; Gordon, M Grace; Subramaniam, Meena; Shamim, Muhammad; Hougen, Kendrick L; Wortman, Ivo; Huang, Su-Chen; Durand, Neva C; Feng, Ting; De Jager, Philip L; Chang, Howard Y; Aiden, Erez Lieberman; Benoist, Christophe; Beer, Michael A; Ye, Chun J; Regev, Aviv.
Afiliação
  • Gate RE; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Cheng CS; Biological and Medical Informatics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
  • Aiden AP; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. chcheng@bu.edu.
  • Siba A; Department of Biology, Boston University, Boston, MA, USA. chcheng@bu.edu.
  • Tabaka M; Department of Molecular and Human Genetics, the Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Lituiev D; Department of Bioengineering, Rice University, Houston, TX, USA.
  • Machol I; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gordon MG; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Subramaniam M; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Shamim M; Department of Molecular and Human Genetics, the Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Hougen KL; Biological and Medical Informatics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
  • Wortman I; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
  • Huang SC; Biological and Medical Informatics Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
  • Durand NC; Department of Molecular and Human Genetics, the Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Feng T; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX, USA.
  • De Jager PL; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
  • Chang HY; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aiden EL; Department of Molecular and Human Genetics, the Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Benoist C; Department of Molecular and Human Genetics, the Center for Genome Architecture, Baylor College of Medicine, Houston, TX, USA.
  • Beer MA; Division of Immunology, Department of Microbiology and Immunology, Harvard Medical School, Boston, MA, USA.
  • Ye CJ; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Regev A; Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology and Psychiatry, Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Nat Genet ; 50(8): 1140-1150, 2018 08.
Article em En | MEDLINE | ID: mdl-29988122
ABSTRACT
Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Linfócitos T CD4-Positivos / Polimorfismo de Nucleotídeo Único Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Cromatina / Linfócitos T CD4-Positivos / Polimorfismo de Nucleotídeo Único Limite: Adult / Female / Humans / Male Idioma: En Ano de publicação: 2018 Tipo de documento: Article