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

Seguín-Estévez, Queralt and Dunand-Sauthier, Isabelle and Lemeille, Sylvain and Iseli, Christian and Ibberson, Mark and Ioannidis, Vassilios and Schmid, Christoph D. and Rousseau, Philippe and Barras, Emmanuèle and Geinoz, Antoine and Xenarios, Ioannis and Acha-Orbea, Hans and Reith, Walter. (2014) Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing. Nucleic acids symposium series, Vol. 42, H. 15. pp. 9641-9655.

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Official URL: http://edoc.unibas.ch/dok/A6298961

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Abstract

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.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Schmid, Christoph
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Oxford University Press
ISSN:0261-3166
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:28
Deposited On:07 Nov 2014 08:28

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