Tada T, Tada M, Hilton K, Barton S C, Sado T, Takagi N, Surani M A
Wellcome/CRC Institute of Cancer and Developmental Biology and Physiological Laboratory, University of Cambridge, Cambridge CB2 1QR, UK.
Dev Genes Evol. 1998 Feb;207(8):551-61. doi: 10.1007/s004270050146.
Expression of imprinted genes is dependent on their parental origin. This is reflected in the heritable differential methylation of parental alleles. The gametic imprints are however reversible as they do not endure for more than one generation. To investigate if the epigenetic changes in male and female germ line are similar or not, we derived embryonic germ (EG) cells from primordial germ cells (PGCs) of day 11.5 and 12.5 male and female embryos. The results demonstrate that they have an equivalent epigenotype. First, chimeras made with EG cells derived from both male and female embryos showed comparable fetal overgrowth and skeletal abnormalities, which are similar to but less severe than those induced by androgenetic embryonic stem (ES) cells. Thus, EG cells derived from female embryos resemble androgenetic ES cells more than parthenogenetic cells. Furthermore, the methylation status of both alleles of a number of loci in EG cells was similar to that of the paternal allele in normal somatic cells. Hence, both alleles of Igf2r region 2, Peg1/Mest, Peg3, Nnat were consistently unmethylated in EG cells as well as in the primary embryonic fibroblasts (PEFs) rescued from chimeras. More strikingly, both alleles of p57kip2 that were also unmethylated in EG cells, underwent de novo methylation in PEFs to resemble a paternal allele in somatic cells. The exceptions were the H19 and Igf2 genes that retained the methylation pattern in PEFs as seen in normal somatic tissues. These studies suggest that the initial epigenetic changes in germ cells of male and female embryos are similar.
印记基因的表达取决于其亲本来源。这反映在亲本等位基因的可遗传差异甲基化上。然而，配子印记是可逆的，因为它们不会持续超过一代。为了研究雄性和雌性生殖系中的表观遗传变化是否相似，我们从第11.5天和12.5天的雄性和雌性胚胎的原始生殖细胞（PGC）中获得了胚胎生殖（EG）细胞。结果表明它们具有相同的表观基因型。首先，用来自雄性和雌性胚胎的EG细胞构建的嵌合体表现出相当的胎儿过度生长和骨骼异常，这与孤雄胚胎干细胞（ES）诱导的异常相似，但程度较轻。因此，来自雌性胚胎的EG细胞比孤雌生殖细胞更类似于孤雄ES细胞。此外，EG细胞中多个位点的两个等位基因的甲基化状态与正常体细胞中父本等位基因的甲基化状态相似。因此，Igf2r区域2、Peg1/Mest、Peg3、Nnat的两个等位基因在EG细胞以及从嵌合体中拯救出的原代胚胎成纤维细胞（PEF）中始终未甲基化。更引人注目的是，p57kip2的两个等位基因在EG细胞中也未甲基化，但在PEF中发生了从头甲基化，类似于体细胞中的父本等位基因。例外的是H19和Igf2基因，它们在PEF中保留了正常体细胞组织中所见的甲基化模式。这些研究表明，雄性和雌性胚胎生殖细胞中的初始表观遗传变化是相似的。
