16788102

pubmed:Citation

7

Cytokine secretion profiles of activated T cells are critical for maintaining the immunologic 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 (IL1A) gene exhibits a stable allele-specific expression pattern in CD4+ T-cell clones. We investigated whether DNA methylation is involved in the allele-specific expression of IL-1alpha. Here, we show that differential methylation of CpGs in the proximal promoter region is associated with allele-specific expression of IL-1alpha in CD4+ T cells. The differential methylation pattern is already observed in naive T cells. In keratinocytes, which constitutively produce IL-1alpha, the proximal promoter is hypomethylated. CpGs located further upstream and in intron 4 were almost all methylated, irrespective of expression. Treatment of nonexpressing cells and of T-cell clones with 5-aza-2'deoxycytidine induced IL-1alpha expression in the nonexpressing 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-1alpha in CD4+ cells is achieved, at least in part, by differential methylation of the promoter.

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http://linkedlifedata.com/resource/pubmed/journal/7603509

http://linkedlifedata.com/resource/pubmed/chemical/Azacitidine, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/decitabine

Oct

pubmed-author:BayleyJean-PierreJP, pubmed-author:GringhuisSonja ISI, pubmed-author:JonesPeter APA, pubmed-author:KooterJan MJM, pubmed-author:VerweijCor LCL, pubmed-author:VerzijlbergenKitty FKF, pubmed-author:WierengaEddy AEA, pubmed-author:van RietschotenJohanna G IJG, pubmed-author:van der Pouw KraanTineke C T MTC

1

NLM

2143-9

pubmed-meshheading:16788102-Alleles, pubmed-meshheading:16788102-Animals, pubmed-meshheading:16788102-Azacitidine, pubmed-meshheading:16788102-CD4-Positive T-Lymphocytes, pubmed-meshheading:16788102-CpG Islands, pubmed-meshheading:16788102-DNA Methylation, pubmed-meshheading:16788102-Enzyme Inhibitors, pubmed-meshheading:16788102-Gene Expression Regulation, pubmed-meshheading:16788102-Humans, pubmed-meshheading:16788102-Interleukin-1, pubmed-meshheading:16788102-Lymphocytes, pubmed-meshheading:16788102-Mice, pubmed-meshheading:16788102-Promoter Regions, Genetic

Differentially methylated alleles in a distinct region of the human interleukin-1alpha promoter are associated with allele-specific expression of IL-1alpha in CD4+ T cells.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural