RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse
RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse
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DOI：
10.1038/nature04674
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发表时间：
2006-05-25
期刊：
影响因子：
64.8
通讯作者：
Cuzin, Francois
中科院分区：
文献类型：
--
作者：
Rassoulzadegan, Minoo;Grandjean, Valerie;Cuzin, Francois
异突变是植物中由等位基因座间的相互作用引起的一种可遗传的表观遗传修饰。在这里，我们报告了一个类似的修改的小鼠试剂盒基因的杂合子与无效突变试剂盒（tm 1Alf）（lacZ插入）的后代。尽管是纯合野生型基因型，但其后代在不同程度上保持Kit突变动物特有的白色斑点。从雄性或雌性亲本有效地遗传，修饰的表型由Kit信使RNA水平的降低以及异常大小的非多聚腺苷酸化RNA分子的积累引起。在减数分裂后阶段持续的转录活性--此时基因通常是沉默的--导致RNA在精子中的积累。将来自Kit（tm 1Alf/+）杂合子的总RNA或Kit特异性microRNA显微注射到受精卵中诱导可遗传的白色尾表型。我们的研究结果确定了一个意想不到的模式与RNA分子的合子转移表观遗传。
Paramutation is a heritable epigenetic modification induced in plants by cross-talk between allelic loci. Here we report a similar modification of the mouse Kit gene in the progeny of heterozygotes with the null mutant Kit(tm1Alf) (a lacZ insertion). In spite of a homozygous wild-type genotype, their offspring maintain, to a variable extent, the white spots characteristic of Kit mutant animals. Efficiently inherited from either male or female parents, the modified phenotype results from a decrease in Kit messenger RNA levels with the accumulation of non-polyadenylated RNA molecules of abnormal sizes. Sustained transcriptional activity at the postmeiotic stages-at which time the gene is normally silent leads to the accumulation of RNA in spermatozoa. Microinjection into fertilized eggs either of total RNA from Kit(tm1Alf/+) heterozygotes or of Kit-specific microRNAs induced a heritable white tail phenotype. Our results identify an unexpected mode of epigenetic inheritance associated with the zygotic transfer of RNA molecules.