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

Seguín-Estévez Q, Dunand-Sauthier I, Lemeille S, Iseli C, Ibberson M, Ioannidis V, Schmid CD, Rousseau P, Barras E, Geinoz A, Xenarios I, Acha-Orbea H, Reith W - Nucleic Acids Res. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.

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Identification of promoters undergoing H4-deacetylation upon Mo-DC maturation. (A) Schematic representation of the ChIP-chip strategy used to identify promoters that are deacetylated in Mo-DCs after 1 h of LPS treatment (top). Representative results for CIITA, IL12B, ACTB, CD1C, CD36 and CLEC4A are provided: signal ratios between 1 h-LPS-treated and untreated Mo-DCs are represented on a log2 scale (bottom left). The percentages of promoters displaying increased or decreased H4Ac are shown (bottom right). (B) Gene-ontology analysis of genes exhibiting LPS-induced H4-deacetylation at their promoters was done using David (http://david.abcc.ncifcrf.gov/). (C) H4-deacetylation (top), nascent transcripts (middle) and pol-II occupancy (bottom) were quantified for the indicated genes in untreated and 1 h-LPS-treated Mo-DCs: results are expressed relative to untreated DCs; nt, not tested. Statistical significance was derived from three experiments: *, P < 0.05, **, P < 0.01, ***, P < 0.001. All measurements were performed in triplicate for each experiment.
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Figure 3: Identification of promoters undergoing H4-deacetylation upon Mo-DC maturation. (A) Schematic representation of the ChIP-chip strategy used to identify promoters that are deacetylated in Mo-DCs after 1 h of LPS treatment (top). Representative results for CIITA, IL12B, ACTB, CD1C, CD36 and CLEC4A are provided: signal ratios between 1 h-LPS-treated and untreated Mo-DCs are represented on a log2 scale (bottom left). The percentages of promoters displaying increased or decreased H4Ac are shown (bottom right). (B) Gene-ontology analysis of genes exhibiting LPS-induced H4-deacetylation at their promoters was done using David (http://david.abcc.ncifcrf.gov/). (C) H4-deacetylation (top), nascent transcripts (middle) and pol-II occupancy (bottom) were quantified for the indicated genes in untreated and 1 h-LPS-treated Mo-DCs: results are expressed relative to untreated DCs; nt, not tested. Statistical significance was derived from three experiments: *, P < 0.05, **, P < 0.01, ***, P < 0.001. All measurements were performed in triplicate for each experiment.

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).


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

Seguín-Estévez Q, Dunand-Sauthier I, Lemeille S, Iseli C, Ibberson M, Ioannidis V, Schmid CD, Rousseau P, Barras E, Geinoz A, Xenarios I, Acha-Orbea H, Reith W - Nucleic Acids Res. (2014)

Identification of promoters undergoing H4-deacetylation upon Mo-DC maturation. (A) Schematic representation of the ChIP-chip strategy used to identify promoters that are deacetylated in Mo-DCs after 1 h of LPS treatment (top). Representative results for CIITA, IL12B, ACTB, CD1C, CD36 and CLEC4A are provided: signal ratios between 1 h-LPS-treated and untreated Mo-DCs are represented on a log2 scale (bottom left). The percentages of promoters displaying increased or decreased H4Ac are shown (bottom right). (B) Gene-ontology analysis of genes exhibiting LPS-induced H4-deacetylation at their promoters was done using David (http://david.abcc.ncifcrf.gov/). (C) H4-deacetylation (top), nascent transcripts (middle) and pol-II occupancy (bottom) were quantified for the indicated genes in untreated and 1 h-LPS-treated Mo-DCs: results are expressed relative to untreated DCs; nt, not tested. Statistical significance was derived from three experiments: *, P < 0.05, **, P < 0.01, ***, P < 0.001. All measurements were performed in triplicate for each experiment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4150779&req=5

Figure 3: Identification of promoters undergoing H4-deacetylation upon Mo-DC maturation. (A) Schematic representation of the ChIP-chip strategy used to identify promoters that are deacetylated in Mo-DCs after 1 h of LPS treatment (top). Representative results for CIITA, IL12B, ACTB, CD1C, CD36 and CLEC4A are provided: signal ratios between 1 h-LPS-treated and untreated Mo-DCs are represented on a log2 scale (bottom left). The percentages of promoters displaying increased or decreased H4Ac are shown (bottom right). (B) Gene-ontology analysis of genes exhibiting LPS-induced H4-deacetylation at their promoters was done using David (http://david.abcc.ncifcrf.gov/). (C) H4-deacetylation (top), nascent transcripts (middle) and pol-II occupancy (bottom) were quantified for the indicated genes in untreated and 1 h-LPS-treated Mo-DCs: results are expressed relative to untreated DCs; nt, not tested. Statistical significance was derived from three experiments: *, P < 0.05, **, P < 0.01, ***, P < 0.001. All measurements were performed in triplicate for each experiment.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Immunology, University of Geneva Medical School, CH-1211 Geneva, Switzerland.

Show MeSH
Related in: MedlinePlus