Vu T H, Hoffman A R
Medical Service, VA Medical Center, Palo Alto, California.
Nature. 1994 Oct 20;371(6499):714-7. doi: 10.1038/371714a0.
Genomic imprinting is a mechanism whereby only one of the two parental alleles is expressed. Loss or relaxation of genomic imprinting has been proposed as an epigenetic mechanism for oncogenesis in a variety of human tumours. Although the mechanism of imprinting is unknown, differential CpG methylation of the parental alleles has been implicated. The human insulin-like growth factor-II (IGF2) gene, which is transcribed from four promoters, P1-P4 (ref. 13), is imprinted in fetal liver but biallelic expression occurs in adult liver. Like most tissues, fetal liver uses primarily promoters P3 and P4 (ref. 17). Adult liver, however, transcribes IGF2 from promoter P1, and it has been suggested that the recruitment of P1 may be responsible for the absence of imprinting in human liver, and in choroid plexus and leptomeninges. We report here that in liver and chondrocytes, IGF2 transcripts from promoter P1 are always derived from both parental alleles, whereas transcripts from promoters P2, P3 and P4 are always from one parental allele. These findings demonstrate that imprinting and a lack of imprinting can both occur within a single gene in a single tissue, suggesting that regional imprinting factors may be important.
基因组印记是一种机制，即两个亲本等位基因中只有一个会表达。基因组印记的缺失或松弛已被认为是多种人类肿瘤发生的一种表观遗传机制。尽管印记机制尚不清楚，但亲本等位基因的差异CpG甲基化与之有关。人类胰岛素样生长因子-II（IGF2）基因从四个启动子P1 - P4转录（参考文献13），在胎儿肝脏中是印记的，但在成人肝脏中是双等位基因表达。与大多数组织一样，胎儿肝脏主要使用启动子P3和P4（参考文献17）。然而，成人肝脏从启动子P1转录IGF2，有人提出P1的募集可能是人类肝脏、脉络丛和软脑膜中缺乏印记的原因。我们在此报告，在肝脏和软骨细胞中，来自启动子P1的IGF2转录本总是来自两个亲本等位基因，而来自启动子P2、P3和P4的转录本总是来自一个亲本等位基因。这些发现表明，印记和缺乏印记可以在单个组织中的单个基因内同时发生，这表明区域印记因子可能很重要。
