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Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing

Seguín-Estévez, Queralt ; Dunand-Sauthier, Isabelle ; Lemeille, Sylvain ; Iseli, Christian ; Ibberson, Mark ; Ioannidis, Vassilios ; Schmid, Christoph D. ; Rousseau, Philippe ; Barras, Emmanuèle ; Geinoz, Antoine ; Xenarios, Ioannis ; Acha-Orbea, Hans ; Reith, Walter

In: Nucleic Acids Research, 2014, vol. 42, no. 15, p. 9641-9655

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    Titre
    • Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing
    Auteur
    • Seguín-Estévez, Queralt. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Dunand-Sauthier, Isabelle. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Lemeille, Sylvain. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Iseli, Christian. Vital-IT, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
    • Ibberson, Mark. Vital-IT, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
    • Ioannidis, Vassilios. Vital-IT, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
    • Schmid, Christoph D.. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4051 Basel, Switzerland
    • Rousseau, Philippe. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Barras, Emmanuèle. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Geinoz, Antoine. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    • Xenarios, Ioannis. Vital-IT, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
    • Acha-Orbea, Hans. Department of Biochemistry, Faculty of Biology and Medicine, University of Lausanne, CH-1066 Epalinges, Switzerland
    • Reith, Walter. Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Nucleic Acids Research, 2014, vol. 42, no. 15, p. 9641-9655. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:301279
    Summary
    The activation, or maturation, of dendritic cells (DCs) is crucial for the initiation of adaptive T-cell mediated immune responses. Research on the molecular mechanisms implicated in DC maturation has focused primarily on inducible gene-expression events promoting the acquisition of new functions, such as cytokine production and enhanced T-cell-stimulatory capacity. In contrast, mechanisms that modulate DC function by inducing widespread gene-silencing remain poorly understood. Yet the termination of key functions is known to be critical for the function of activated DCs. Genome-wide analysis of activation-induced histone deacetylation, combined with genome-wide quantification of activation-induced silencing of nascent transcription, led us to identify a novel inducible transcriptional-repression pathway that makes major contributions to the DC-maturation process. This silencing response is a rapid primary event distinct from repression mechanisms known to operate at later stages of DC maturation. The repressed genes function in pivotal processes—including antigen-presentation, extracellular signal detection, intracellular signal transduction and lipid-mediator biosynthesis—underscoring the central contribution of the silencing mechanism to rapid reshaping of DC function. Interestingly, promoters of the repressed genes exhibit a surprisingly high frequency of PU.1-occupied sites, suggesting a novel role for this lineage-specific transcription factor in marking genes poised for inducible repression