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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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Mapping of PU.1-binding in Mo-DC. (A) Relative expression (mRNA-sequencing) of mRNAs encoding ETS family members in immature Mo-DCs. (B) PU.1-ocuppied sites (ChIP-sequencing) were analyzed in the promoter regions of genes that are deacetylated and silenced >5-fold (left column), induced >5-fold (center column), or exhibit no change in expression (right column) in Mo-DCs after 1 h of LPS treatment. Panels show the percent of genes having at least 1 PU.1 peak within a window of the indicated size centered on the TSS (first row), the percent of genes containing at least 1 PU.1 peak within the indicated distance upstream or downstream of the TSS (second row), heat maps indicating the positions of PU.1 peaks (black lines) within 4 kb regions centered on the TSS (third row) and the percent of genes having at least one PU.1 peak situated at the indicated distance upstream or downstream of the TSS (bottom row). In all graphs, the entire set of human genes was used as baseline reference. RPKM, reads per kb per million.
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Figure 6: Mapping of PU.1-binding in Mo-DC. (A) Relative expression (mRNA-sequencing) of mRNAs encoding ETS family members in immature Mo-DCs. (B) PU.1-ocuppied sites (ChIP-sequencing) were analyzed in the promoter regions of genes that are deacetylated and silenced >5-fold (left column), induced >5-fold (center column), or exhibit no change in expression (right column) in Mo-DCs after 1 h of LPS treatment. Panels show the percent of genes having at least 1 PU.1 peak within a window of the indicated size centered on the TSS (first row), the percent of genes containing at least 1 PU.1 peak within the indicated distance upstream or downstream of the TSS (second row), heat maps indicating the positions of PU.1 peaks (black lines) within 4 kb regions centered on the TSS (third row) and the percent of genes having at least one PU.1 peak situated at the indicated distance upstream or downstream of the TSS (bottom row). In all graphs, the entire set of human genes was used as baseline reference. RPKM, reads per kb per million.

Mentions: PU.1 is the most strongly expressed ETS-family member in Mo-DCs (Figure 6A and Supplementary Table S2). ChIP-sequencing experiments were performed to map PU.1 binding in Mo-DCs. The distribution of PU.1-bound sites was compared between the promoter regions of genes that are deacetylated-silenced, induced or unchanged in their expression in response to LPS (Figure 6B). The promoters of all human genes were used as baseline. PU.1-occupied sites were more frequent relative to baseline in all three subsets, distributed symmetrically upstream and downstream of the TSS, and enriched most strongly near the TSS. Surprisingly, PU.1-bound sites were most frequent in deacetylated-silenced genes. Binding was not affected by LPS treatment at most positions, indicating that silencing is not due to PU.1-disengagement (Supplementary Figure S5).


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)

Mapping of PU.1-binding in Mo-DC. (A) Relative expression (mRNA-sequencing) of mRNAs encoding ETS family members in immature Mo-DCs. (B) PU.1-ocuppied sites (ChIP-sequencing) were analyzed in the promoter regions of genes that are deacetylated and silenced >5-fold (left column), induced >5-fold (center column), or exhibit no change in expression (right column) in Mo-DCs after 1 h of LPS treatment. Panels show the percent of genes having at least 1 PU.1 peak within a window of the indicated size centered on the TSS (first row), the percent of genes containing at least 1 PU.1 peak within the indicated distance upstream or downstream of the TSS (second row), heat maps indicating the positions of PU.1 peaks (black lines) within 4 kb regions centered on the TSS (third row) and the percent of genes having at least one PU.1 peak situated at the indicated distance upstream or downstream of the TSS (bottom row). In all graphs, the entire set of human genes was used as baseline reference. RPKM, reads per kb per million.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 6: Mapping of PU.1-binding in Mo-DC. (A) Relative expression (mRNA-sequencing) of mRNAs encoding ETS family members in immature Mo-DCs. (B) PU.1-ocuppied sites (ChIP-sequencing) were analyzed in the promoter regions of genes that are deacetylated and silenced >5-fold (left column), induced >5-fold (center column), or exhibit no change in expression (right column) in Mo-DCs after 1 h of LPS treatment. Panels show the percent of genes having at least 1 PU.1 peak within a window of the indicated size centered on the TSS (first row), the percent of genes containing at least 1 PU.1 peak within the indicated distance upstream or downstream of the TSS (second row), heat maps indicating the positions of PU.1 peaks (black lines) within 4 kb regions centered on the TSS (third row) and the percent of genes having at least one PU.1 peak situated at the indicated distance upstream or downstream of the TSS (bottom row). In all graphs, the entire set of human genes was used as baseline reference. RPKM, reads per kb per million.
Mentions: PU.1 is the most strongly expressed ETS-family member in Mo-DCs (Figure 6A and Supplementary Table S2). ChIP-sequencing experiments were performed to map PU.1 binding in Mo-DCs. The distribution of PU.1-bound sites was compared between the promoter regions of genes that are deacetylated-silenced, induced or unchanged in their expression in response to LPS (Figure 6B). The promoters of all human genes were used as baseline. PU.1-occupied sites were more frequent relative to baseline in all three subsets, distributed symmetrically upstream and downstream of the TSS, and enriched most strongly near the TSS. Surprisingly, PU.1-bound sites were most frequent in deacetylated-silenced genes. Binding was not affected by LPS treatment at most positions, indicating that silencing is not due to PU.1-disengagement (Supplementary Figure S5).

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