Genomic imprinting in mice: its function and mechanism.
Genomic imprinting in mice: its function and mechanism.
复制标题
DOI：
10.1095/biolreprod54.2.273
复制
发表时间：
1996-02
影响因子：
3.6
通讯作者：
Philip A. Leighton;Jennifer R. Saam;R. Ingram;Shirley M. Tilghman
中科院分区：
文献类型：
--
作者：
Philip A. Leighton;Jennifer R. Saam;R. Ingram;Shirley M. Tilghman
基因组印记是一个基因的两个亲本等位基因差异表达的一种表观遗传现象。虽然基因组印记的功能尚不清楚，但有人提出它在哺乳动物中进化以调节子宫内生长。这一建议与旨在揭示小鼠7号染色体基因组印迹的机制和影响的实验一致，该区域包含四个印迹基因：Mash-2（转录因子）和H19（非编码RNA）是母系表达的，而胰岛素-2 （in-2）和胰岛素样生长因子2 （Igf-2）是父系表达的。在小鼠中产生了两个位点的靶向破坏；这些都支持了H19基因的功能是建立Igf-2和Ins-2的印记的假设。母体染色体上的H19转录通过一种机制排除了其他两个基因的转录，这种机制涉及对一组共同增强子的竞争。在父系染色体上，H19基因被DNA甲基化沉默，从而允许其他基因使用增强子。
Genomic imprinting is an epigenetic phenomenon by which the two parental alleles of a gene are differentially expressed. Although the function of genomic imprinting is not clear, it has been proposed that it evolved in mammals to regulate intrauterine growth. This proposal is consistent with experiments that were designed to reveal the mechanism and impact of genomic imprinting in a region of mouse chromosome 7 that contains four imprinted genes: Mash-2 (a transcription factor) and H19 (a noncoding RNA) are maternally expressed, whereas Insulin-2 (Ins-2) and Insulin-like growth factor 2 (Igf-2) are paternally expressed. Two targeted disruptions at the locus were generated in mice; these support the hypothesis that the function of the H19 gene is to set up the imprinting of both Igf-2 and Ins-2. H19 transcription on the maternal chromosome precludes transcription of the other two genes by a mechanism that involves competition for a common set of enhancers. On the paternal chromosome the H19 gene is silenced by DNA methylation, thus permitting the use of enhancers by the other genes.