Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Hum Mol Genet. 2012 Feb 1;21(3):548-58. doi: 10.1093/hmg/ddr488. Epub 2011 Oct 24.
Within the vertebrate groups, only mammals are subject to a specialized epigenetic process termed genomic imprinting in which genes are preferentially expressed from one parental allele. Imprinted expression has been reported for >100 mouse genes and, for approximately one-quarter of these genes, the imprinted expression is specific to the placenta (or extraembryonic tissues). This seemingly placenta-specific imprinted expression has garnered much attention, as has the apparent lack of conserved imprinting between the human and mouse placenta. In this study, we used a novel approach to re-investigate the placenta-specific expression using embryo transfer and trophoblast stem cells. We analyzed 20 genes previously reported to show maternal allele-specific expression in the placenta, and only 8 genes were confirmed to be imprinted. Other genes were likely to be falsely identified as imprinted due to their relatively high expression in contaminating maternal cells. Next, we performed a genome-wide transcriptome assay and identified 133 and 955 candidate imprinted genes with paternal allele- and maternal allele-specific expression. Of those we analyzed in detail, 1/6 (Gab1) of the candidates for paternal allele-specific expression and only 1/269 (Ano1) candidates for maternal allele-specific expression were authentically imprinted genes. Imprinting of Ano1 and Gab1 was specific to the placenta and neither gene displayed allele-specific promoter DNA methylation. Imprinting of ANO1, but not GAB1, was conserved in the human placenta. Our findings impose a considerable revision of the current views of placental imprinting.
在脊椎动物中，只有哺乳动物会经历一种称为基因组印记的专门表观遗传过程，其中基因优先从一个亲本等位基因表达。已经报道了 >100 个小鼠基因的印记表达，并且对于这些基因中的大约四分之一，印记表达是胎盘特有的（或胚胎外组织）。这种看似胎盘特异性的印记表达引起了很多关注，就像人类和小鼠胎盘之间缺乏保守的印记一样。在这项研究中，我们使用胚胎转移和滋养层干细胞的新方法重新研究了胎盘特异性表达。我们分析了 20 个先前报道在胎盘上表现出母本等位基因特异性表达的基因，只有 8 个基因被证实是印记的。其他基因可能由于其在污染的母体细胞中相对较高的表达而被错误地鉴定为印记。接下来，我们进行了全基因组转录组分析，鉴定出 133 个和 955 个候选父本等位基因特异性表达和母本等位基因特异性表达的印记基因。在我们详细分析的那些基因中，候选父本等位基因特异性表达的基因中有 1/6（Gab1）和候选母本等位基因特异性表达的基因中只有 1/269（Ano1）是真正的印记基因。Ano1 和 Gab1 的印记是胎盘特异性的，并且这两个基因都没有表现出等位基因特异性启动子 DNA 甲基化。ANO1 的印记，而不是 GAB1 的印记，在人类胎盘中有保守性。我们的发现对当前关于胎盘印记的观点进行了相当大的修正。
