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

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Item Type:	Article
Title:	Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells
Creators Name:	Steinfelder, S., Floess, S., Engelbert, D., Haeringer, B., Baron, U., Rivino, L., Steckel, B., Gruetzkau, A., Olek, S., Geginat, J., Huehn, J. and Hamann, A.
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.
Keywords:	CCR6 Receptors, Cell Separation, DNA Methylation, Flow Cytometry, Gene Expression, Gene Expression Regulation, Genetic Epigenesis, Polymerase Chain Reaction, T-Lymphocytes, Transfection
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	117
Number:	10
Page Range:	2839-2846
Date:	10 March 2011
Official Publication:	https://doi.org/10.1182/blood-2010-06-293027
PubMed:	View item in PubMed

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