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.
Falek
P R
PR
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Ben-Sasson
S Z
SZ
Ariel
M
M
D000818:Animals; D019175:DNA Methylation; D004262:DNA Restriction Enzymes / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D015847:Interleukin-4; D007371:Interferon-gamma; D004262:DNA Restriction Enzymes