Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads.
Analysis of DNA methylation acquisition at the imprinted Dlk1 locus reveals asymmetry at CpG dyads.
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DOI：
10.1186/1756-8935-7-9
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发表时间：
2014
影响因子：
3.9
通讯作者：
Davis TL
中科院分区：
文献类型：
--
作者：
Gagne A;Hochman A;Qureshi M;Tong C;Arbon J;McDaniel K;Davis TL
印记基因亲本等位基因上 DNA 甲基化的差异分布将等位基因彼此区分开，并决定了其亲本起源特异性表达模式。虽然初级印记控制区的差异 DNA 甲基化是通过配子遗传的，但在胚胎发育过程中，次级位点获得了额外的等位基因特异性 DNA 甲基化，并在维持基因组印记中发挥作用。这种体细胞 DNA 甲基化在次级位点建立的精确机制尚未明确定义，并且可能会有所不同，因为不同印记簇中的基因在这些位点获得甲基化发生在不同时间。在这项研究中，我们发现单个印记簇内多个位点的体细胞 DNA 甲基化获取时间也存在差异。父本等位基因特异性 DNA 甲基化最初是在植入后发育的相似阶段在相连的 Dlk1 和 Gtl2 差异甲基化区域 (DMR) 处获得的。相反，与 Gtl2-DMR 不同，母体 Dlk1-DMR 在成体组织中获得 DNA 甲基化。这些数据表明 Dlk1/Gtl2 印记簇中 DNA 甲基化的获取是可变的。我们进一步发现 Dlk1 差异甲基化区域表现出较低的 DNA 甲基化保真度，大约三分之一的甲基化 CpG 二联体存在半甲基化就证明了这一点。我们假设，次级差异甲基化位点的 DNA 甲基化维持效率可能低于初级印记控制区域。
Differential distribution of DNA methylation on the parental alleles of imprinted genes distinguishes the alleles from each other and dictates their parent of origin-specific expression patterns. While differential DNA methylation at primary imprinting control regions is inherited via the gametes, additional allele-specific DNA methylation is acquired at secondary sites during embryonic development and plays a role in the maintenance of genomic imprinting. The precise mechanisms by which this somatic DNA methylation is established at secondary sites are not well defined and may vary as methylation acquisition at these sites occurs at different times for genes in different imprinting clusters. In this study, we show that there is also variability in the timing of somatic DNA methylation acquisition at multiple sites within a single imprinting cluster. Paternal allele-specific DNA methylation is initially acquired at similar stages of post-implantation development at the linked Dlk1 and Gtl2 differentially methylated regions (DMRs). In contrast, unlike the Gtl2-DMR, the maternal Dlk1-DMR acquires DNA methylation in adult tissues. These data suggest that the acquisition of DNA methylation across the Dlk1/Gtl2 imprinting cluster is variable. We further found that the Dlk1 differentially methylated region displays low DNA methylation fidelity, as evidenced by the presence of hemimethylation at approximately one-third of the methylated CpG dyads. We hypothesize that the maintenance of DNA methylation may be less efficient at secondary differentially methylated sites than at primary imprinting control regions.
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由GTL2 5'区域中插入诱变引起的DLK1-GTL2基因座的印迹丧失。
影响因子：
2.9
作者：
Steshina, Ekaterina Y.;Carr, Michael S.;Glick, Elena A.;Yevtodiyenko, Aleksey;Appelbe, Oliver K.;Schmidt, Jennifer V.
通讯作者：
Schmidt, Jennifer V.
影响因子：
5.3
作者：
Tremblay, KD;Duran, KL;Bartolomei, MS
通讯作者：
Bartolomei, MS
影响因子：
9.2
作者：
Takada, S;Tevendale, M;Ferguson-Smith, AC
通讯作者：
Ferguson-Smith, AC
影响因子：
4.8
作者：
Vilkaitis, G;Suetake, I;Tajima, S
通讯作者：
Tajima, S
影响因子：
7
作者：
Paulsen, M;Takada, S;Ferguson-Smith, AC
通讯作者：
Ferguson-Smith, AC