A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival
A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival
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DOI：
10.1016/s1074-7613(01)00227-8
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发表时间：
2001-11-01
期刊：
影响因子：
32.4
通讯作者：
Wilson, CB
中科院分区：
文献类型：
--
作者：
Lee, PP;Fitzpatrick, DR;Wilson, CB
DNA甲基化和维持DNA甲基转移酶Dnmt 1在发育阶段和细胞系特异性基因表达的表观遗传调控中的作用尚不确定。这是解决这里通过产生的小鼠，其中Dnmt 1被灭活的Cre/loxP介导的删除在T细胞发育的顺序阶段。在早期双阴性胸腺细胞中Dnmt 1的缺失导致TCR α β（+）细胞存活受损和非典型CD 8（+）TCR γ δ（+）细胞的产生。双阳性胸腺细胞中Dnmt 1的缺失损害了活化诱导的增殖，但差异增强了幼稚外周T细胞的细胞因子mRNA表达。我们的结论是，Dnmt 1和DNA甲基化是必要的某些基因的正确表达，定义命运，并确定T细胞的功能。
The role of DNA methylation and of the maintenance DNA methyltransferase Dnmt1 in the epigenetic regulation of developmental stage- and cell lineage-specific gene expression in vivo is uncertain. This is addressed here through the generation of mice in which Dnmt1 was inactivated by Cre/loxP-mediated deletion at sequential stages of T cell development. Deletion of Dnmt1 in early double-negative thymocytes led to impaired survival of TCR alpha beta (+) cells and the generation of atypical CD8(+)TCR gamma delta (+) cells. Deletion of Dnmt1 in double-positive thymocytes impaired activation-induced proliferation but differentially enhanced cytokine mRNA expression by naive peripheral T cells. We conclude that Dnmt1 and DNA methylation are required for the proper expression of certain genes that define fate and determine function in T cells.