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首页> 外文期刊>Molecular and Cellular Biology >Specific Differentially Methylated Domain Sequences Direct the Maintenance of Methylation at Imprinted Genes
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Specific Differentially Methylated Domain Sequences Direct the Maintenance of Methylation at Imprinted Genes

机译：特定的差异甲基化域序列指导印迹基因的甲基化维持。

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摘要

Landmark features of imprinted genes are differentially methylated domains (DMDs), in which one parental allele is methylated on CpG dinucleotides and the opposite allele is unmethylated. Genetic experiments in the mouse have shown that DMDs are required for the parent-specific expression of linked clusters of imprinted genes. To understand the mechanism whereby the differential methylation is established and maintained, we analyzed a series of transgenes containing DMD sequences and showed that imperfect tandem repeats from DMDs associated with the Snurf/Snrpn, Kcnq1, and Igf2r gene clusters govern transgene imprinting. For the Igf2r DMD the minimal imprinting signal is two unit copies of the tandem repeat. This imprinted transgene behaves identically to endogenous imprinted genes in Dnmt1o and Dnmt3L mutant mouse backgrounds. The primary function of the imprinting signal within the transgene DMD is to maintain, during embryogenesis and a critical period of genomic reprogramming, parent-specific DNA methylation states established in the germ line. This work advances our understanding of the imprinting mechanism by defining a genomic signal that dependably perpetuates an epigenetic state during postzygotic development.
机译：印迹基因的标志性特征是差异甲基化域（DMD），其中一个亲本等位基因在CpG二核苷酸上被甲基化，而相反的等位基因未甲基化。小鼠的遗传实验表明，DMDs是印迹基因连锁簇的亲本特异性表达所必需的。为了了解建立和维持差异甲基化的机制，我们分析了一系列含有DMD序列的转基因，并发现与 Snurf / Snrpn ， Kcnq1 相关的DMD的不完美串联重复序列。 em>和 Igf2r 基因簇控制转基因印迹。对于 Igf2r DMD，最小印迹信号是串联重复序列的两个单位副本。此印迹的转基因与 Dnmt10 和 Dnmt3L 突变小鼠背景中的内源印迹基因具有相同的行为。转基因DMD中的印迹信号的主要功能是在胚发生和基因组重编程的关键时期内维持种系中建立的亲本特异性DNA甲基化状态。这项工作通过定义在后合子发育过程中可靠地延续表观遗传状态的基因组信号，提高了我们对印迹机制的理解。

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