Fitzpatrick D R, Shirley K M, Kelso A
Leukocyte Biology Unit, Queensland Institute of Medical Research, Joint Transplantation Biology Program, University of Queensland, Brisbane, Australia. davidFqimr.edu.au
J Immunol. 1999 May 1;162(9):5053-7.
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.
基因组DNA甲基化模式影响细胞分化过程中功能的发育和维持。如果以表观遗传方式遗传，调控序列的甲基化可对基因表达产生持久影响。最近的研究表明，DNA甲基化在原代T淋巴细胞中细胞因子基因的差异表达中起调节作用。在这里，我们通过克隆谱系分析表明，IFN-γ启动子中的甲基化模式在CD44高CD8 + T细胞及其后代中表现出长期稳定的遗传，经历了16次细胞分裂和5个数量级的克隆扩增。此外，在T细胞刺激撤除和可检测到的IFN-γ mRNA丧失后，去甲基化的IFN-γ启动子被稳定遗传，这与被动而非主动维持机制一致。这代表了一种具有明确表观遗传特征的稳定细胞记忆形式，可能有助于维持T细胞细胞因子表达模式和T细胞记忆。
