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J Leukoc Biol. 2008 Sep;84(3):824-34. doi: 10.1189/jlb.0807583. Epub 2008 Jun 27.

Epigenetic mechanisms of age-dependent KIR2DL4 expression in T cells.

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  • 1Kathleen B. and Mason I. Lowance Center for Human Immunology and Rheumatology, Emory University School of Medicine, 101 Woodruff Circle, #1003, Atlanta, GA 30322, USA.

Abstract

Killer Ig-like receptor (KIR) expression is mostly restricted to NK cells controlling their activation. With increasing age, KIRs are expressed on T cells and contribute to age-related diseases. We examined epigenetic mechanisms that determine the competency of T cells to transcribe KIR2DL4. Compared with Jurkat cells and CD4(+)CD28(+) T cells from young individuals, DNA methyltransferase (DNMT) inhibition was strikingly more effective in T cells from elderly adults and the CD4(+)CD28(-) T cell line HUT78 to induce KIR2DL4 transcription. In these susceptible cells, the KIR2DL4 promoter was partially demethylated, and dimethylated H3-Lys 4 was increased, and all other histone modifications were characteristic for an inactive promoter. In comparison, NK cells had a fully demethylated KIR2DL4 promoter and the full spectrum of histone modifications indicative of active transcription with H3 and H4 acetylation, di- and trimethylated H3-Lys 4, and reduced, dimethylated H3-Lys 9. These results suggest that an increased competency of T cells to express KIR2DL4 with aging is conferred by a selective increase in H3-Lys 4 dimethylation and limited DNA demethylation. The partially accessible promoter is sensitive to DNMT inhibition, which is sufficient to induce full transcription without further histone acetylation and methylation.

PMID:
18586981
[PubMed - indexed for MEDLINE]
PMCID:
PMC2516893
Free PMC Article
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