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

Item Type:	Article
Title:	Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells
Creators Name:	Steinfelder, S. and Floess, S. and Engelbert, D. and Haeringer, B. and Baron, U. and Rivino, L. and Steckel, B. and Gruetzkau, A. and Olek, S. and Geginat, J. and 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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