title: Cutting edge: stable epigenetic inheritance of regional IFN-gamma promoter demethylation in CD44highCD8+ T lymphocytes.
abstract: Genomic DNA methylation patterns influence the development and maintenance of function during cellular differentiation. Methylation of regulatory sequences can have long-lasting effects on gene expression if inherited in an epigenetic manner. Recent work suggests that DNA methylation has a regulatory role in differential cytokine gene expression in primary T lymphocytes. Here we show, by clonal lineage analysis, that methylation patterns in the IFN-gamma promoter exhibit long term faithful inheritance in CD44highCD8+ T cells and their progeny, through 16 cell divisions and a clonal expansion of 5 orders of magnitude. Moreover, the demethylated IFN-gamma promoter is faithfully inherited following the withdrawal of T cell stimulation and the loss of detectable IFN-gamma mRNA, consistent with passive rather than active maintenance mechanisms. This represents a form of stable cellular memory, of defined epigenetic characteristics, that may contribute to the maintenance of T cell cytokine expression patterns and T cell memory.
authors.affiliation: Leukocyte Biology Unit, Queensland Institute of Medical Research, Joint Transplantation Biology Program, University of Queensland, Brisbane, Australia. davidFqimr.edu.au
authors.forename: D R
authors.initials: DR
authors.lastname: Fitzpatrick
authors.forename: K M
authors.initials: KM
authors.lastname: Shirley
authors.forename: A
authors.initials: A
authors.lastname: Kelso
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019175:DNA Methylation; D005786:Gene Expression Regulation / Q000276:immunology; D018960:Hyaluronan Receptors / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
chemical_list: D018960:Hyaluronan Receptors; D007371:Interferon-gamma