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Limited evolutionary conservation of imprinting in the human placenta

机译：人类胎盘印迹的有限进化保护

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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.
机译：基因组印记的表观遗传现象提供了额外水平的基因调节，该水平仅限于有限数量的基因，这对胚胎发育常常是（但并非唯一）重要。烙印的发展和维持与将母亲资源分配给发育中的胎儿与母亲的福祉之间的平衡有关。印在胚胎和胚外组织中的基因在小鼠和人类之间显示出广泛的保守性。在这里，我们检查了仅印在胎盘中的小鼠基因的人类直系同源基因，分析了等位基因特异性表达和表观遗传修饰。从早孕滋养细胞到足月胎，KCNQ1结构域的基因以及印迹基因Gatm和Dcn的分离的人类直向同源物均在人体内等位表达。这种印迹的缺乏独立于启动子CpG甲基化，并且与H3赖氨酸-9残基（H3K9me2）的等位基因组修饰二甲基化和H3赖氨酸-27残基的三甲基化（H3K27me3）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出多态一致表达，只有少数样品显示出印迹。这些发现共同对理解哺乳动物基因组印迹的演变具有重要意义。由于大多数人的怀孕都是单胎，因此缺乏竞争可能解释了人对胎盘特异性烙印的需求相对宽松。

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