PARENTAL LEGACY DETERMINES METHYLATION AND EXPRESSION OF AN AUTOSOMAL TRANSGENE - A MOLECULAR MECHANISM FOR PARENTAL IMPRINTING

PARENTAL LEGACY DETERMINES METHYLATION AND EXPRESSION OF AN AUTOSOMAL TRANSGENE - A MOLECULAR MECHANISM FOR PARENTAL IMPRINTING
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DOI:
10.1016/0092-8674(87)90330-8
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发表时间:
1987-08-28
期刊:
影响因子:
64.5
通讯作者:
LEDER, P
LEDER, P
中科院分区:
生物学1区
文献类型:
--
作者:
SWAIN, JL;STEWART, TA;LEDER, P

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我们已经创建了一个转基因小鼠品系,其中一个常染色体转基因轴承元件的RSV LTR和易位的c-myc基因遵守非常不寻常的规则。如果转基因是从父本遗传的,它在心脏中表达,而不是其他组织。如果它是从母本遗传的,它根本不会表达。这种表达模式与所有组织中明显的亲代印记甲基化状态精确相关。转基因的甲基化通过其通过雌性亲本获得,并在雄性配子发生期间消除。这些观察结果提供了直接的分子证据,即常染色体基因的表达可能取决于遗传该基因的父母的性别。它们还提供了一个合理的机制,了解父母的印记,可能是相关的哺乳动物孤雌生殖的失败,一些常染色体基因的明显的非孟德尔行为,甲基化在基因调控中的作用。
We have created a transgenic mouse strain in which an autosomal transgene bearing elements of the RSV LTR and a translocated c-myc gene obeys very unusual rules. If the transgene is inherited from the male parent, it is expressed in the heart and no other tissue. If it is inherited from the female parent, it is not expressed at all. This pattern of expression correlates precisely with a parentally imprinted methylation state evident in all tissues. Methylation of the transgene is acquired by its passage through the female parent and eliminated during gametogenesis in the male. These observations provide direct molecular evidence that autosomal gene expression can depend upon the sex of the parent from which the gene is inherited. They also provide a plausible mechanism for understanding parental imprinting that may be relevant to the failure of parthenogenesis in mammals, the apparent non-Mendelian behavior of some autosomal genes, and the role of methylation in gene regulation.