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

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Serval ID
serval:BIB_33FC79D5A0AA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing.
Journal
Nucleic Acids Research
Author(s)
Seguín-Estévez Q., Dunand-Sauthier I., Lemeille S., Iseli C., Ibberson M., Ioannidis V., Schmid C.D., Rousseau P., Barras E., Geinoz A., Xenarios I., Acha-Orbea H., Reith W.
ISSN
1362-4962 (Electronic)
ISSN-L
0305-1048
Publication state
Published
Issued date
2014
Volume
42
Number
15
Pages
9641-9655
Language
english
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.
Pubmed
Web of science
Open Access
Yes
Create date
20/11/2014 11:37
Last modification date
20/08/2019 14:20
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