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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2143-2149.
Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2006-01-021147.
 Previous Article | Next Article 
Submitted January 26, 2006
Accepted May 22, 2006
Differentially methylated alleles in a distinct region of
the human interleukin-1 promoter are associated
with allele-specific expression of IL-1 in
CD4+ T cells
Johanna G van Rietschoten*, Kitty F Verzijlbergen, Sonja I Gringhuis, Tineke C van der Pouw Kraan, Jean-Pierre Bayley, Eddy A Wierenga, Peter A Jones, Jan M Kooter, and Cor L Verweij
Dept. of Molecular Cell Biology & Immunology, VU University /Norris Comprehensive Cancer Center, USC
Dept. of Molecular Cell Biology & Immunology, VU University Medical Center (VUMC)
Dept. of Human Genetics, Leiden University Medical Center
Dept. of Cell Biology and Histology, Academic Medical Center (AMC), University of Amsterdam
Dept. of Urology, Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center
Dept. of Genetics, Vrije Universiteit (VU)
* Corresponding author; email: annavanrietschoten{at}gmail.com.
Cytokine secretion profiles of activated T cells are critical for maintaining the immunological balance between protection and tolerance. In mice, several cytokines have been reported to exhibit monoallelic expression. Previously, we found that the human interleukin-1 alpha (IL-1 ) gene exhibits a stable allele-specific expression pattern in CD4+ T cell clones. We have investigated whether DNA methylation is involved in the allele-specific expression of IL-1. Here, we show that differential methylation of CpGs in the proximal promoter region is associated with allele-specific expression of IL-1 in CD4+ T cells. The differential methylation pattern is already observed in naive T cells. In keratinocytes, which constitutively produce IL-1, the proximal promoter is hypomethylated. CpGs located further upstream and in intron 4 were almost all methylated, irrespective of expression. Treatment of non-expressing cells and of T cell clones with 5-aza-2’ deoxycytidine induced IL-1 expression in the non-expressing cells and induced expression of the formerly silent allele in T cell clones. In addition, electrophoretic mobility shift assays showed that methylation of CpGs in the proximal promoter resulted in direct inhibition of binding of nuclear factor(s). Taken together, these results suggest that allele-specific expression of IL-1 in CD4+ cells is achieved at least in part, by differential methylation of the promoter.
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