Rassoulzadegan Minoo, Grandjean Valérie, Gounon Pierre, Vincent Stéphane, Gillot Isabelle, Cuzin François
Inserm, U636, F-06108 Nice, France.
Nature. 2006 May 25;441(7092):469-74. doi: 10.1038/nature04674.
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.
副突变是植物中由等位基因座之间的串扰诱导产生的一种可遗传的表观遗传修饰。在此，我们报道了在携带无效突变体Kit(tm1Alf)（lacZ插入）的杂合子后代中，小鼠Kit基因发生了类似的修饰。尽管其基因型为纯合野生型，但它们的后代在不同程度上保留了Kit突变动物特有的白斑。这种修饰后的表型可从雄性或雌性亲本高效遗传，其原因是Kit信使RNA水平降低，同时积累了异常大小的非多聚腺苷酸化RNA分子。减数分裂后阶段的持续转录活性（此时该基因通常处于沉默状态）导致精子中RNA的积累。将Kit(tm1Alf/+)杂合子的总RNA或Kit特异性微小RNA显微注射到受精卵中，均可诱导出可遗传的白尾表型。我们的结果确定了一种与RNA分子的合子转移相关的意外表观遗传遗传模式。
