Imprinting of PEG1/MEST isoform 2 in human placenta
Imprinting of PEG1/MEST isoform 2 in human placenta
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DOI：
10.1016/j.placenta.2004.12.003
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发表时间：
2006-02-01
期刊：
影响因子：
3.8
通讯作者：
Tycko, B
中科院分区：
文献类型：
--
作者：
McMinn, J;Wei, M;Tycko, B
PEG 1基因（又称PEG 1基因）MEST）在人胎盘滋养层和内皮细胞中表达，来自敲除小鼠的数据显示该基因调节胎盘和胎儿生长。PEG 1 mRNA的亚型1起始于外显子1c，并产生MEST蛋白的长型。这种亚型是印记的，在许多人类和小鼠器官（包括胎盘）中仅从父系等位基因表达。相比之下，PEG 1同种型2，起始于外显子1a并产生短形式的MEST蛋白，是双等位基因的。在几个非胎盘器官中表达（非印记）。在这里，我们表明，PEG 1亚型2实际上是印记在一个大的子集的人类胎盘。与PEG 1外显子1a重叠的CpG岛在各种胎儿和成人非胎盘组织中是未甲基化的，但在胎盘中通常是基本上甲基化的，其中大系列中的甲基化程度接近正态分布。亚硫酸氢盐转化/测序表明，个体间差异反映了高度甲基化与未甲基化等位基因的相对代表性，RT-PCR/RFLP分析显示，在大多数胎盘中，PEG 1亚型2 mRNA的等位基因表达存在强烈偏倚，甲基化等位基因比例较高。这些数据突出了PEG 1亚型2作为未来研究个体间表观遗传变异及其与人类胎盘和胎儿生长关系的标志物。(c)2005爱思唯尔有限公司保留所有权利。
The PEG1 gene (a.k.a. MEST) is expressed in human placental trophoblast and endothelium, and data from knockout mice show that this gene regulates placental and fetal growth. Isoform 1 of PEG1 mRNA initiates from exon 1c and produces the long form of the MEST protein. This isoform is imprinted, with expression only from the paternal allele in many human and mouse organs, including placenta. In contrast, PEG1 isoform 2, initiating from exon la and producing the short form of MEST protein, is biallelically. expressed (non-imprinted) in several non-placental organs. Here we show that PEG1 isoform 2 is in fact imprinted in a large subset of human placentae. A CpG island overlapping PEG1 exon la is unmethylated in various fetal and adult non-placental tissues, but is often substantially methylated in the placenta, with the extent of methylation in a large series approximating a normal distribution. Bisulfite conversion/sequencing indicates that the inter-individual differences reflect the relative representation of heavily methylated vs. unmethylated alleles, and RT-PCR/RFLP analysis shows strongly biased allelic expression of PEG1 isoform 2 mRNA in a majority of placentae with a high proportion of methylated alleles. These data highlight PEG1 isoform 2 as a marker for future studies of inter-individual epigenetic variation and its relation to placental and fetal growth in humans. (c) 2005 Elsevier Ltd. All rights reserved.