Evidence for Epigenetic Maintenance of Ly49a Monoallelic Gene Expression1
Evidence for Epigenetic Maintenance of Ly49a Monoallelic Gene Expression1
复制标题
Ly49a 单等位基因表达的表观遗传维持的证据1
作者：
A. Rouhi;L. Gagnier;F. Takei;D. Mager
虽然在结构上不相关，但人杀伤细胞Ig样（KIR）基因和啮齿动物凝集素样Ly 49基因在NK细胞中发挥相似的功能作用。此外，这两个基因家族显示杂色，单等位基因表达模式建立在转录水平上。DNA甲基化在维持具有CpG岛启动子的KIR基因的表达模式中起重要作用。DNA甲基化在Ly 49基因表达中的潜在作用尚不清楚，Ly 49基因具有CpG缺失的启动子。在这项研究中，我们表明，低甲基化的区域包括Pro-2的Ly 49 a和Ly 49 c在原代C57 BL/6 NK细胞启动子与基因的表达。使用C57 BL/6 × BALB/c F1杂交小鼠，我们证明了Ly 49 a的表达等位基因是低甲基化的，而非表达等位基因是高度甲基化的，表明表观遗传学在维持单等位基因Ly 49基因表达中的作用。此外，Ly 49 a Pro-2区域在胎儿NK细胞中高度甲基化，但在非淋巴组织中高度甲基化。最后，在明显的对比KIR基因，我们表明，DNA甲基化和组蛋白乙酰化状态的Pro-2区域与Ly 49 a的表达状态严格相连。
Although structurally unrelated, the human killer cell Ig-like (KIR) genes and the rodent lectin-like Ly49 genes serve similar functional roles in NK cells. Moreover, both gene families display variegated, monoallelic expression patterns established at the transcriptional level. DNA methylation has been shown to play an important role in maintenance of expression patterns of KIR genes, which have CpG island promoters. The potential role of DNA methylation in expression of Ly49 genes, which have CpG-poor promoters, is unknown. In this study, we show that hypomethylation of the region encompassing the Pro-2 promoter of Ly49a and Ly49c in primary C57BL/6 NK cells correlates with expression of the gene. Using C57BL/6 × BALB/c F1 hybrid mice, we demonstrate that the expressed allele of Ly49a is hypomethylated while the nonexpressed allele is heavily methylated, indicating a role for epigenetics in maintaining monoallelic Ly49 gene expression. Furthermore, the Ly49a Pro-2 region is heavily methylated in fetal NK cells but variably methylated in nonlymphoid tissues. Finally, in apparent contrast to the KIR genes, we show that DNA methylation and the histone acetylation state of the Pro-2 region are strictly linked with Ly49a expression status.
影响因子：
3.5
作者：
B. Shykind
通讯作者：
B. Shykind