Liu Jing-He, Zhu Jia-Qiao, Liang Xing-Wei, Yin Shen, Ola Safiriyu Idowu, Hou Yi, Chen Da-Yuan, Schatten Heide, Sun Qing-Yuan
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Genomics. 2008 Feb;91(2):121-8. doi: 10.1016/j.ygeno.2007.10.005. Epub 2007 Nov 26.
Epigenetic modifications are closely associated with embryo developmental potential. One of the epigenetic modifications thought to be involved in genomic imprinting is DNA methylation. Here we show that the maternally imprinted genes Snrpn and Peg1/Mest were nearly unmethylated or heavily methylated, respectively, in their differentially methylated regions (DMRs) at the two-cell stage in parthenogenetic embryos. However, both genes were gradually de novo methylated, with almost complete methylation of all CpG sites by the morula stage in parthenogenetic embryos. Unexpectedly, another maternally imprinted gene, Peg3, showed distinct dynamics of methylation during preimplantation development of diploid parthenogenetic embryos. Peg3 showed seemingly normal methylation patterns at the two-cell and morula stages, but was also strongly de novo methylated in parthenogenetic blastocysts. In contrast, the paternally imprinted genes H19 and Rasgrf1 showed complete unmethylation of their DMRs at the morula stage in parthenogenetic embryos. These results indicate that diploid parthenogenetic embryos adopt a maternal-type methylation pattern on both sets of maternal chromosomes and that the aberrantly homogeneous status of methylation imprints may partially account for developmental failure.
表观遗传修饰与胚胎发育潜能密切相关。DNA甲基化是一种被认为参与基因组印记的表观遗传修饰。在此我们表明,在孤雌生殖胚胎的二细胞阶段,母源印记基因Snrpn和Peg1/Mest在其差异甲基化区域(DMRs)分别几乎未甲基化或高度甲基化。然而,在孤雌生殖胚胎中,这两个基因均逐渐发生从头甲基化,到桑椹胚阶段所有CpG位点几乎完全甲基化。出乎意料的是,另一个母源印记基因Peg3在二倍体孤雌生殖胚胎的着床前发育过程中显示出独特的甲基化动态。Peg3在二细胞和桑椹胚阶段显示出看似正常的甲基化模式,但在孤雌生殖囊胚中也强烈地从头甲基化。相比之下,父源印记基因H19和Rasgrf1在孤雌生殖胚胎的桑椹胚阶段其DMRs完全未甲基化。这些结果表明,二倍体孤雌生殖胚胎在两组母源染色体上都采用母源型甲基化模式,并且甲基化印记的异常均一状态可能部分解释了发育失败的原因。