Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse differentially methylated regions (DMRs): paternally methylated DMRs contain less CpGs than maternally methylated DMRs
Bisulfite sequencing and dinucleotide content analysis of 15 imprinted mouse differentially methylated regions (DMRs): paternally methylated DMRs contain less CpGs than maternally methylated DMRs
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DOI：
10.1159/000090824
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发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Sasaki, H.
中科院分区：
文献类型：
--
作者：
Kobayashi, H.;Suda, C.;Sasaki, H.
哺乳动物中的印记基因显示依赖于亲本来源的单等位基因表达，并且通常与差异甲基化区域（DMR）相关。DMR分为两类：初级DMR在精子发生或卵子发生中获得配子特异性甲基化，并在整个发育过程中保持等位基因甲基化差异;次级DMR在受精后建立差异甲基化模式。一些主要DMR的靶向破坏表明，它们决定了附近印迹基因的等位基因表达和二级DMR的等位基因甲基化的建立。然而，主要DMR是如何识别的印记机制是未知的。作为阐明原代DMR序列特征的一步，我们通过亚硫酸氢盐测序确定了12.5-dpc胚胎中15种原代小鼠DMR（包括12种母系甲基化和3种父系甲基化DMR）的范围和边界。我们发现，DMR的平均大小为3.2 kb，其平均G+C含量为54%。DMR序列的二核苷酸含量分析显示，尽管它们通常富含CpG，但父系甲基化DMR比母系甲基化DMR含有更少的CpG。我们的研究结果提供了一个基础，为进一步表征的DMR。版权所有（c）2006 S. Karger AG，巴塞尔。
Imprinted genes in mammals show monoallelic expression dependent on parental origin and are often associated with differentially methylated regions (DMRs). There are two classes of DMR: primary DMRs acquire gamete-specific methylation in either spermatogenesis or oogenesis and maintain the allelic methylation differences throughout development; secondary DMRs establish differential methylation patterns after fertilization. Targeted disruption of some primary DMRs showed that they dictate the allelic expression of nearby imprinted genes and the establishment of the allelic methylation of secondary DMRs. However, how primary DMRs are recognized by the imprinting machinery is unknown. As a step toward elucidating the sequence features of the primary DMRs, we have determined the extents and boundaries of 15 primary mouse DMRs (including 12 maternally methylated and three paternally methylated DMRs) in 12.5-dpc embryos by bisulfite sequencing. We found that the average size of the DMRs was 3.2 kb and that their average G+C content was 54%. Dinucleotide content analysis of the DMR sequences revealed that, although they are generally CpG rich, the paternally methylated DMRs contain less CpGs than the maternally methylated DMRs. Our findings provide a basis for the further characterization of DMRs. Copyright (c) 2006 S. Karger AG, Basel.