ROLE FOR DNA METHYLATION IN GENOMIC IMPRINTING
ROLE FOR DNA METHYLATION IN GENOMIC IMPRINTING
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DOI：
10.1038/366362a0
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发表时间：
1993-11-25
期刊：
影响因子：
64.8
通讯作者：
JAENISCH, R
中科院分区：
文献类型：
--
作者：
LI, E;BEARD, C;JAENISCH, R
父本和母本基因组并不相同，两者都是哺乳动物发育所必需的1,2。亲本基因组之间的差异被认为是由于配子特异性差异修饰所致，这一过程称为基因组印记。转基因甲基化的研究表明，甲基化模式可以以亲本特异性方式遗传3-7，这表明DNA甲基化可能在基因组印记中发挥作用。最近发现三个印记基因 H19、胰岛素样生长因子 2 (Igf-2) 和 Igf-2 受体 (Igf-2r) 中的 CpG 岛（或位点）根据其亲本起源而被差异甲基化8-12，这强化了 DNA 甲基化在基因组印记中的功能意义。我们检查了这三个印记基因在 DNA 甲基转移酶活性缺陷的突变小鼠中的表达13。我们在这里报告，所有三个基因的表达在突变胚胎中都受到影响：H19基因的通常沉默的父本等位基因被激活，而Igf-2基因的通常活跃的父本等位基因和Igf-2r基因的活跃母本等位基因被抑制。我们的结果表明，控制印记基因的父本和母本等位基因的差异表达需要正常水平的DNA甲基化。
THE paternal and maternal genomes are not equivalent and both are required for mammalian development1,2. The difference between the parental genomes is believed to be due to gamete-specific differential modification, a process known as genomic imprinting. The study of transgene methylation has shown that methylation patterns can be inherited in a parent-of-origin-specific manner3-7, suggesting that DNA methylation may play a role in genomic imprinting. The functional significance of DNA methylation in genomic imprinting was strengthened by the recent finding that CpG islands (or sites) in three imprinted genes, H19, insulin-like growth factor 2 (Igf-2), and Igf-2 receptor (Igf-2r), are differentially methylated depending on their parental origin8-12. We have examined the expression of these three imprinted genes in mutant mice that are deficient in DNA methyltransferase activity13. We report here that expression of all three genes was affected in mutant embryos: the normally silent paternal allele of the H19 gene was activated, whereas the normally active paternal allele of die Igf-2 gene and the active maternal allele of the Igf-2r gene were repressed. Our results demonstrate that a normal level of DNA methylation is required for controlling differential expression of the paternal and maternal alleles of imprinted genes.