DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors.
DNA methylation inhibition increases T cell KIR expression through effects on both promoter methylation and transcription factors.
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DOI：
10.1016/j.clim.2008.08.009
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Richardson B
中科院分区：
文献类型：
--
作者：
Liu Y;Kuick R;Hanash S;Richardson B
杀伤细胞免疫球蛋白样受体（KIR）基因是在NK细胞上表达的多态性家族，并且“衰老的”CD 28- T细胞与心血管疾病有关。KIR启动子是高度同源的，并且NK表达受DNA甲基化调控。T细胞KIR调控知之甚少。我们询问表观遗传机制和/或转录因子改变是否决定T细胞KIR表达。DNA甲基化抑制激活正常T细胞中的多个KIR基因。选择KIR 2DL 2和KIR 2DL 4用于进一步研究。两者的表达都与启动子去甲基化有关，而报告构建体中启动子的甲基化抑制了表达。KIR报告构建体表达也增加去甲基化的T细胞和所需的Ets 1，Sp1和AML位点，这意味着对转录因子的影响。这在Sp1中得到了证实。这些结果表明，在大多数T细胞中，KIR基因被DNA甲基化抑制，DNA去甲基化通过影响染色质结构和转录因子促进其表达。
Killer-cell immunoglobulin-like receptor (KIR) genes are a polymorphic family expressed on NK cells, and “senescent” CD28- T cells implicated in cardiovascular disease. KIR promoters are highly homologous, and NK expression is regulated by DNA methylation. T cell KIR regulation is poorly understood. We asked if epigenetic mechanisms and/or transcription factor alterations determine T cell KIR expression. DNA methylation inhibition activated multiple KIR genes in normal T cells. KIR2DL2 and KIR2DL4 were selected for further study. Expression of both was associated with promoter demethylation, and methylation of the promoters in reporter constructs suppressed expression. KIR reporter construct expression also increased in demethylated T cells and required Ets1, Sp1 and AML sites, implying effects on transcription factors. This was confirmed for Sp1. These results indicate that KIR genes are suppressed by DNA methylation in most T cells, and DNA demethylation promotes their expression through effects on both chromatin structure and transcription factors.
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作者：
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通讯作者：
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