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|Title:||Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells||Authors:||Steinfelder, S.
|Issue Date:||10-Mar-2011||Citation:||Steinfelder, S., Floess, S., Engelbert, D., Haeringer, B., Baron, U., Rivino, L., Steckel, B., Gruetzkau, A., Olek, S., Geginat, J., Huehn, J., Hamann, A. (2011-03-10). Epigenetic modification of the human CCR6 gene is associated with stable CCR6 expression in T cells. Blood 117 (10) : 2839-2846. ScholarBank@NUS Repository. https://doi.org/10.1182/blood-2010-06-293027||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. © 2011 by The American Society of Hematology.||Source Title:||Blood||URI:||http://scholarbank.nus.edu.sg/handle/10635/126725||ISSN:||00064971||DOI:||10.1182/blood-2010-06-293027|
|Appears in Collections:||Staff Publications|
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