Correlation between DNA methylation and murine IFN-gamma and IL-4 expression

In order to determine the possible role of DNA methylation as a regulatory mechanism for the restricted pattern of lymphokine production among differentiated Th(1)and Th(2)cells, we examined the extent of methylation of the interferon gamma (IFN-gamma) and the interleukin 4 (IL-4) genes in fresh activated murine Th(0), Th(1)and Th(2)cells, unstimulated naive T cells, B cells, bone marrow derived non-B non-T cells, thymocytes and liver. All of the CpG dinucleotides examined in the IL-4 and the IFN-gamma genes, were fully methylated over the body of the gene in all of the examined cells. However, analysis of the promoter regions of these genes revealed a different pattern. While the IL-4 promoter is fully methylated in all of the examined cells, two adjacent CpG dinucleotides near the initiation point of the IFN-gamma gene were unmethylated in all T cells, including 17-day-old fetal thymocytes. In contrast, B cells, bone marrow non-B non-T cells and liver cells displayed a full methylated profile of the IFNgamma promoter. These results suggest that the mutually exclusive pattern of IFNgamma and IL-4 production in Th(1)and Th(2)cells is not regulated by differential demethylation of these two genes.