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Domains of genome-wide gene expression dysregulation in Down's syndrome.
Letourneau, Audrey; Santoni, Federico A; Bonilla, Ximena; Sailani, M Reza; Gonzalez, David; Kind, Jop; Chevalier, Claire; Thurman, Robert; Sandstrom, Richard S; Hibaoui, Youssef; Garieri, Marco; Popadin, Konstantin; Falconnet, Emilie; Gagnebin, Maryline; Gehrig, Corinne; Vannier, Anne; Guipponi, Michel; Farinelli, Laurent; Robyr, Daniel; Migliavacca, Eugenia; Borel, Christelle; Deutsch, Samuel; Feki, Anis; Stamatoyannopoulos, John A; Herault, Yann; van Steensel, Bas; Guigo, Roderic; Antonarakis, Stylianos E.
Afiliación
  • Letourneau A; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2].
  • Santoni FA; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2].
  • Bonilla X; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Sailani MR; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Gonzalez D; Center for Genomic Regulation, University Pompeu Fabra, 08003 Barcelona, Spain.
  • Kind J; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
  • Chevalier C; AneuPath 21, Institut de Génétique Biologie Moléculaire et Cellulaire, Translational medicine and Neuroscience program, IGBMC, ICS, PHENOMIN, CNRS, INSERM, Université de Strasbourg, UMR7104, UMR964, 1 rue Laurent Fries, 67404 Illkirch, France.
  • Thurman R; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  • Sandstrom RS; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  • Hibaoui Y; Stem Cell Research Laboratory, Department of Obstetrics and Gynecology, Geneva University Hospitals, 1211 Geneva, Switzerland.
  • Garieri M; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Popadin K; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Falconnet E; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Gagnebin M; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Gehrig C; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Vannier A; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Guipponi M; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Farinelli L; FASTERIS SA, 1228 Plan-les-Ouates, Switzerland.
  • Robyr D; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Migliavacca E; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] Swiss Institute of Bioinfomatics, 1211 Geneva, Switzerland.
  • Borel C; Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland.
  • Deutsch S; DOE Joint Genome Institute, Walnut Creek, California 94598, USA.
  • Feki A; Stem Cell Research Laboratory, Department of Obstetrics and Gynecology, Geneva University Hospitals, 1211 Geneva, Switzerland.
  • Stamatoyannopoulos JA; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA.
  • Herault Y; AneuPath 21, Institut de Génétique Biologie Moléculaire et Cellulaire, Translational medicine and Neuroscience program, IGBMC, ICS, PHENOMIN, CNRS, INSERM, Université de Strasbourg, UMR7104, UMR964, 1 rue Laurent Fries, 67404 Illkirch, France.
  • van Steensel B; Division of Gene Regulation, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
  • Guigo R; Center for Genomic Regulation, University Pompeu Fabra, 08003 Barcelona, Spain.
  • Antonarakis SE; 1] Department of Genetic Medicine and Development, University of Geneva Medical School, University Hospitals of Geneva, 1211 Geneva, Switzerland [2] iGE3 Institute of Genetics and Genomics of Geneva, 1211 Geneva, Switzerland.
Nature ; 508(7496): 345-50, 2014 Apr 17.
Article en En | MEDLINE | ID: mdl-24740065
Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins is organized in domains along all chromosomes that are either upregulated or downregulated. These gene expression dysregulation domains (GEDDs) can be defined by the expression level of their gene content, and are well conserved in induced pluripotent stem cells derived from the twins' fibroblasts. Comparison of the transcriptome of the Ts65Dn mouse model of Down's syndrome and normal littermate mouse fibroblasts also showed GEDDs along the mouse chromosomes that were syntenic in human. The GEDDs correlate with the lamina-associated (LADs) and replication domains of mammalian cells. The overall position of LADs was not altered in trisomic cells; however, the H3K4me3 profile of the trisomic fibroblasts was modified and accurately followed the GEDD pattern. These results indicate that the nuclear compartments of trisomic cells undergo modifications of the chromatin environment influencing the overall transcriptome, and that GEDDs may therefore contribute to some trisomy 21 phenotypes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Genoma / Síndrome de Down / Transcriptoma Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación de la Expresión Génica / Genoma / Síndrome de Down / Transcriptoma Límite: Animals / Female / Humans / Male Idioma: En Revista: Nature Año: 2014 Tipo del documento: Article Pais de publicación: Reino Unido