The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice
The human HYMAI/PLAGL1 differentially methylated region acts as an imprint control region in mice
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DOI：
10.1016/j.ygeno.2006.07.005
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发表时间：
2006-11-01
期刊：
影响因子：
4.4
通讯作者：
Kono, Tomohiro
中科院分区：
文献类型：
--
作者：
Arima, Takahiro;Yamasaki, Katsuhisa;Kono, Tomohiro
印迹中心（IC）是指在生殖细胞中被识别的顺式元件，通过表观遗传学修饰可以在体细胞中产生完整的印迹程序。两个父系表达的人类基因，HYMAI和PLAGL 1（LOT 1/ZAC），位于人类染色体6 q24内。在该区域内存在一个1-kb的CpG岛，其在小鼠的体细胞中差异甲基化，在精子中未甲基化，在成熟卵母细胞中甲基化，这是IC的特征。在患有短暂性新生儿糖尿病的患者中观察到人类同源区域的甲基化缺失，并且超甲基化与多种癌症相关，这表明该区域调节该区域中参与这些疾病的一个或多个关键基因的表达。我们现在报道，携带人HYMA 1/PLAGL 1 DMR的转基因在小鼠中以正确的亲本来源特异性方式被甲基化，这足以赋予转基因的印迹表达。因此，我们认为该DMR作为HYMAI/PLAGL 1结构域的IC发挥作用。(c)2006年爱思唯尔公司All rights reserved.
Imprinting centers (IC) can be defined as cis-elements that are recognized in the germ line and are epigenetically modified to bring about the full imprinting program in a somatic cell. Two paternally expressed human genes, HYMAI and PLAGL1 (LOT1/ZAC), are located within human chromosome 6q24. Within this region lies a 1-kb CpG island that is differentially methylated in somatic cells, unmethylated in sperm, and methylated in mature oocytes in mice, characteristic features of an IC. Loss of methylation of the homologous region in humans is observed in patients with transient neonatal diabetes mellitus and hypermethylation is associated with a variety of cancers, suggesting that this region regulates the expression of one or more key genes in this region involved in these diseases. We now report that a transgene carrying the human HYMA1/PLAGL1 DMR was methylated in the correct parent-origin-specific manner in mice and this was sufficient to confer imprinted expression from the transgene. Therefore, we propose that this DMR functions as the IC for the HYMAI/PLAGL1 domain. (c) 2006 Elsevier Inc. All rights reserved.