Smallwood Alan, Papageorghiou Aris, Nicolaides Kypros, Alley M K R, Jim Alice, Nargund Geeta, Ojha Kamal, Campbell Stuart, Banerjee Subhasis
Harris Birthright Research Centre for Fetal Medicine, King's College Hospital Medical School, London SE5 9RS, United Kingdom.
Biol Reprod. 2003 Jul;69(1):286-93. doi: 10.1095/biolreprod.102.013078. Epub 2003 Mar 5.
Maternally imprinted PEG10 and SGCE, separated by approximately 2.15 Mb from Syncytin (HERV-W) gene at 7q21.3, are implicated in choriocarcinoma and Silver-Russell syndrome. Here we have analyzed the temporal regulation of mRNA expression of these genes in placenta and demonstrate that Syncytin gene activation is highest in term placenta, PEG10, downregulated at early hypoxic phase, and highly activated at 11-12 wk of gestation. In contrast, transcription from SGCE remained unchanged throughout pregnancy, suggesting two neighboring imprinted genes are differentially regulated at very early pregnancy. Additionally, accumulation of two major species of mRNA (8 kb and 3.1 kb) encoded by HERV-W in placenta is regulated: 3.1 kb mRNA level remained unchanged throughout pregnancy, whereas the production of 8 kb species was highest in term placenta. Western blot and immunohistochemical staining of placental tissues with monoclonal antibodies revealed a marked reduction of syncytin glycoprotein synthesis in late pregnancy. Therefore, the relative levels of 3.1 kb and 8 kb mRNAs in trophoblasts could regulate syncytin protein synthesis, possibly by competition of the two mRNA species for translational apparatus.
母系印记的PEG10和SGCE基因位于7q21.3,与合胞素(HERV-W)基因相距约2.15 Mb,它们与绒毛膜癌和Silver-Russell综合征有关。在此,我们分析了这些基因在胎盘中mRNA表达的时间调控,结果表明合胞素基因在足月胎盘中的激活程度最高,PEG10在早期缺氧阶段下调,在妊娠11 - 12周时高度激活。相比之下,SGCE的转录在整个孕期保持不变,这表明两个相邻的印记基因在妊娠早期受到不同的调控。此外,胎盘内由HERV-W编码的两种主要mRNA(8 kb和3.1 kb)的积累也受到调控:3.1 kb mRNA水平在整个孕期保持不变,而8 kb mRNA在足月胎盘中的产生量最高。用单克隆抗体对胎盘组织进行蛋白质免疫印迹和免疫组织化学染色显示,妊娠晚期合胞素糖蛋白的合成显著减少。因此,滋养层细胞中3.1 kb和8 kb mRNA的相对水平可能通过这两种mRNA竞争翻译装置来调节合胞素蛋白的合成。