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

Published inNucleic acids research, vol. 42, no. 15, p. 9641-9655
Publication date2014
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.

Citation (ISO format)
SEGUIN ESTÉVEZ, Maria Queralt et al. Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing. In: Nucleic acids research, 2014, vol. 42, n° 15, p. 9641–9655. doi: 10.1093/nar/gku674
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ISSN of the journal0305-1048
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