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Expression in Human T Cells via DNA Methylation1Department of Internal Medicine, Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520
IL-7 is critical for the development and survival of T cells. Recently, we found two subsets of human CD8+ T cells expressing IL-7R
high and IL-7Rlow with different cell survival responses to IL-7. Although these CD8+ T cell subsets have differential IL-7R gene expression, the mechanism for this is unknown. DNA methylation is an important gene regulatory mechanism and is associated with the inactivation of gene expression. Thus, we investigated a role for DNA methylation in differentially regulating IL-7R gene expression in human CD8+ T cells and Jurkat T cells. IL-7RhighCD8+ T cells had decreased methylation in the IL-7R gene promoter compared with IL-7RlowCD8+ T cells and Jurkat T cells with low levels of IL-7R. Treating Jurkat T cells with 5-aza-2'-deoxycytidine, which reduced DNA methylation, increased IL-7R expression. Plus, the unmethylated IL-7R gene promoter construct had higher levels of promoter activity than the methylated one as measured by a luciferase reporter assay. These findings suggest that DNA methylation is involved in regulating IL-7R expression in T cells via affecting IL-7R gene promoter activity, and that the methylation of this gene promoter could be a potential target for modifying IL-7-mediated T cell development and survival.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from the National Institutes of Health (K08 AR49444-02), the American College of Rheumatology, the Arthritis Foundation, the American Foundation for Aging Research, and Claude D. Pepper Older Americans Independence Center at Yale University School of Medicine (P30AG21342 NIH/NIA).
2 Address correspondence and reprint requests to Dr. Insoo Kang, Department of Internal Medicine, Section of Rheumatology TAC S541C, Yale School of Medicine, P.O. Box 208031, New Haven, CT 06520. E-mail address: Insoo.kang{at}yale.edu
3 Abbreviations used in this paper: Dnmt, DNA methyltransferase; 5-aza-dC, 5-aza-2'-deoxycytidine; EM, effector memory; GABP, guanine- and adenine-binding protein ; GFI-1, growth factor independence 1.
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