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Chromatin three-dimensional interactions mediate genetic effects on gene expression.
Delaneau, O; Zazhytska, M; Borel, C; Giannuzzi, G; Rey, G; Howald, C; Kumar, S; Ongen, H; Popadin, K; Marbach, D; Ambrosini, G; Bielser, D; Hacker, D; Romano, L; Ribaux, P; Wiederkehr, M; Falconnet, E; Bucher, P; Bergmann, S; Antonarakis, S E; Reymond, A; Dermitzakis, E T.
Affiliation
  • Delaneau O; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
  • Zazhytska M; Swiss Institute of Bioinformatics (SIB), University of Geneva, Geneva, Switzerland.
  • Borel C; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.
  • Giannuzzi G; Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
  • Rey G; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
  • Howald C; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.
  • Kumar S; Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
  • Ongen H; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
  • Popadin K; Swiss Institute of Bioinformatics (SIB), University of Geneva, Geneva, Switzerland.
  • Marbach D; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.
  • Ambrosini G; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
  • Bielser D; Swiss Institute of Bioinformatics (SIB), University of Geneva, Geneva, Switzerland.
  • Hacker D; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.
  • Romano L; Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Ribaux P; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
  • Wiederkehr M; Department of Genetic Medicine and Development, University of Geneva, Geneva, Switzerland.
  • Falconnet E; Swiss Institute of Bioinformatics (SIB), University of Geneva, Geneva, Switzerland.
  • Bucher P; Institute of Genetics and Genomics in Geneva, University of Geneva, Geneva, Switzerland.
  • Bergmann S; Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
  • Antonarakis SE; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
  • Reymond A; School of Life Science, Immanuel Kant Federal Baltic University, Kaliningrad, Russia.
  • Dermitzakis ET; Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Science ; 364(6439)2019 05 03.
Article in En | MEDLINE | ID: mdl-31048460
ABSTRACT
Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromatin / Gene Expression Regulation Limits: Humans Language: En Journal: Science Year: 2019 Type: Article Affiliation country: Switzerland
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Chromatin / Gene Expression Regulation Limits: Humans Language: En Journal: Science Year: 2019 Type: Article Affiliation country: Switzerland