Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/325088
Title:
Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells.
Authors:
Steinfelder, Svenja; Floess, Stefan; Engelbert, Dirk; Haeringer, Barbara; Baron, Udo; Rivino, Laura; Steckel, Bodo; Gruetzkau, Andreas; Olek, Sven; Geginat, Jens; Huehn, Jochen; Hamann, Alf
Abstract:
CCR6 is a chemokine receptor expressed on Th17 cells and regulatory T cells that is induced by T-cell priming with certain cytokines, but how its expression and stability are regulated at the molecular level is largely unknown. Here, we identified and characterized a noncoding region of the human CCR6 locus that displayed unmethylated CpG motifs (differentially methylated region [DMR]) selectively in CCR6(+) lymphocytes. CCR6 expression on circulating CD4(+) T cells was stable on cytokine-induced proliferation but partially down-regulated on T-cell receptor stimulation. However, CCR6 down-regulation was mostly transient, and the DMR within the CCR6 locus remained demethylated. Notably, in vitro induction of CCR6 expression with cytokines in T-cell receptor-activated naive CD4(+) T cells was not associated with a demethylated DMR and resulted in unstable CCR6 expression. Conversely, treatment with the DNA methylation inhibitor 5'-azacytidine induced demethylation of the DMR and led to increased and stable CCR6 expression. Finally, when cloned into a reporter gene plasmid, the DMR displayed transcriptional activity in memory T cells that was suppressed by DNA methylation. In summary, we have identified a noncoding region of the human CCR6 gene with methylation-sensitive transcriptional activity in CCR6(+) T cells that controls stable CCR6 expression via epigenetic mechanisms.
Affiliation:
Dept. of experimental immunology, Helmholtz Centre for infection reseach, Inhoffenstr. 7, D38124 Braunschweig, Germany.
Citation:
Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells. 2011, 117 (10):2839-46 Blood
Journal:
Blood
Issue Date:
10-Mar-2011
URI:
http://hdl.handle.net/10033/325088
DOI:
10.1182/blood-2010-06-293027
PubMed ID:
21228329
Type:
Article
Language:
en
ISSN:
1528-0020
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorSteinfelder, Svenjaen
dc.contributor.authorFloess, Stefanen
dc.contributor.authorEngelbert, Dirken
dc.contributor.authorHaeringer, Barbaraen
dc.contributor.authorBaron, Udoen
dc.contributor.authorRivino, Lauraen
dc.contributor.authorSteckel, Bodoen
dc.contributor.authorGruetzkau, Andreasen
dc.contributor.authorOlek, Svenen
dc.contributor.authorGeginat, Jensen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorHamann, Alfen
dc.date.accessioned2014-08-22T13:02:39Z-
dc.date.available2014-08-22T13:02:39Z-
dc.date.issued2011-03-10-
dc.identifier.citationEpigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells. 2011, 117 (10):2839-46 Blooden
dc.identifier.issn1528-0020-
dc.identifier.pmid21228329-
dc.identifier.doi10.1182/blood-2010-06-293027-
dc.identifier.urihttp://hdl.handle.net/10033/325088-
dc.description.abstractCCR6 is a chemokine receptor expressed on Th17 cells and regulatory T cells that is induced by T-cell priming with certain cytokines, but how its expression and stability are regulated at the molecular level is largely unknown. Here, we identified and characterized a noncoding region of the human CCR6 locus that displayed unmethylated CpG motifs (differentially methylated region [DMR]) selectively in CCR6(+) lymphocytes. CCR6 expression on circulating CD4(+) T cells was stable on cytokine-induced proliferation but partially down-regulated on T-cell receptor stimulation. However, CCR6 down-regulation was mostly transient, and the DMR within the CCR6 locus remained demethylated. Notably, in vitro induction of CCR6 expression with cytokines in T-cell receptor-activated naive CD4(+) T cells was not associated with a demethylated DMR and resulted in unstable CCR6 expression. Conversely, treatment with the DNA methylation inhibitor 5'-azacytidine induced demethylation of the DMR and led to increased and stable CCR6 expression. Finally, when cloned into a reporter gene plasmid, the DMR displayed transcriptional activity in memory T cells that was suppressed by DNA methylation. In summary, we have identified a noncoding region of the human CCR6 gene with methylation-sensitive transcriptional activity in CCR6(+) T cells that controls stable CCR6 expression via epigenetic mechanisms.en
dc.language.isoenen
dc.rightsArchived with thanks to Blooden
dc.subject.meshCell Separationen
dc.subject.meshDNA Methylationen
dc.subject.meshEpigenesis, Geneticen
dc.subject.meshFlow Cytometryen
dc.subject.meshGene Expressionen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHumansen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshReceptors, CCR6en
dc.subject.meshT-Lymphocytesen
dc.subject.meshTransfectionen
dc.titleEpigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells.en
dc.typeArticleen
dc.contributor.departmentDept. of experimental immunology, Helmholtz Centre for infection reseach, Inhoffenstr. 7, D38124 Braunschweig, Germany.en
dc.identifier.journalBlooden

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