Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing.
Bottom Line: 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.
Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.Show MeSH
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Mentions: To identify additional genes subjected to the same silencing process as CIITA, H4Ac-ChIP samples from immature Mo-DCs and 1 h-LPS-treated Mo-DCs were used to probe genomic arrays carrying a comprehensive set of human promoters (Figure 3A). ∼1000 promoters (∼4%) exhibited strong and reproducible H4-deacetylation (Figure 3A, Supplementary Figure S2A). Promoters exhibiting H4-deacetylation were more numerous than those displaying increased H4Ac (Figure 3A, ∼1%). The spatial distribution of deacetylated regions revealed a preference for positions close to the transcription-start-site (TSS, Supplementary Figure S2C). ChIP-chip experiments performed with our custom array confirmed that H4-deacetylation affected regions upstream of the TSSs of representative genes (Supplementary Figure S2B).
Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.