Limited evolutionary conservation of imprinting in the human placenta
Limited evolutionary conservation of imprinting in the human placenta
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DOI：
10.1073/pnas.0511031103
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发表时间：
2006-04-25
影响因子：
11.1
通讯作者：
Moore, GE
中科院分区：
文献类型：
--
作者：
Monk, D;Arnaud, P;Moore, GE
基因组印记的表观遗传现象提供了一个额外的水平的基因调控，这是局限于有限数量的基因，经常，但不是唯一的，重要的胚胎发育。印迹的进化和维持与母体资源分配给发育中的胎儿和母体健康之间的平衡有关。在胚胎和胚胎外组织中都有印记的基因在老鼠和人类之间表现出广泛的保守性。在这里，我们研究了仅在胎盘中印迹的小鼠基因的人类同源物，分析了等位基因特异性表达和表观遗传修饰。KCNQ1结构域的基因和印迹基因Gatm和Dcn的分离的人类同源基因都在人类中双等位表达，从妊娠早期的滋养细胞到足月。这种印迹的缺失与启动子CpG甲基化无关，并与H3赖氨酸-9残基的二甲基化（H3K9me2）和H3赖氨酸-27残基的三甲基化（H3K27me3）的等位基因组蛋白修饰的缺失相关。这些特定的组蛋白修饰被认为有助于调节小鼠的印迹。来自IGF2R结构域的基因在胎盘中显示多态性一致表达，仅在少数样本中显示有印迹。这些发现对理解哺乳动物基因组印记的进化具有重要意义。因为大多数人类怀孕都是单胎，这种竞争的缺失可能解释了人类对胎盘特异性印记的相对宽松的需求。
The epigenetic phenomenon of genomic imprinting provides an additional level of gene regulation that is confined to a limited number of genes, frequently, but not exclusively, important for embryonic development. The evolution and maintenance of imprinting has been linked to the balance between the allocation of maternal resources to the developing fetus and the mother's well being. Genes that are imprinted in both the embryo and extraembryonic tissues show extensive conservation between a mouse and a human. Here we examine the human orthologues of mouse genes imprinted only in the placenta, assaying allele-specific expression and epigenetic modifications. The genes from the KCNQ1 domain and the isolated human orthologues of the imprinted genes Gatm and Dcn all are expressed biallelically in the human, from first-trimester trophoblast through to term. This lack of imprinting is independent of promoter CpG methylation and correlates with the absence of the allelic histone modifications dimethylation of lysine-9 residue of H3 (H3K9me2) and trimethylation of lysine-27 residue of H3 (H3K27me3). These specific histone modifications are thought to contribute toward regulation of imprinting in the mouse. Genes from the IGF2R domain show polymorphic concordant expression in the placenta, with imprinting demonstrated in only a minority of samples. Together these findings have important implications for understanding the evolution of mammalian genomic imprinting. Because most human pregnancies are singletons, this absence of competition might explain the comparatively relaxed need in the human for placental-specific imprinting.