Imprinting analysis of the mouse chromosome 7C region inDNMT1-null embryos
Imprinting analysis of the mouse chromosome 7C region inDNMT1-null embryos
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DNMT1 缺失胚胎中小鼠染色体 7C 区域的印记分析
DOI：
10.1016/j.gene.2014.10.006
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发表时间：
2014
期刊：
影响因子：
3.5
通讯作者：
Kishino T
中科院分区：
文献类型：
--
作者：
Nakagaki A;Osanai H;Kishino T
小鼠染色体7 C，与人类15 q11-q13正交，具有印记结构域，其中大多数基因仅从父系等位基因表达。印迹结构域包含父本表达基因Snurf/Snrpn、Ndn、Magel 2、Mkrn 3和Frat 3、C/D-box小核仁RNA（snoRNA）和母本表达基因Ube 3a。在这个大的（约3-4 Mb）域的印记表达是由一个双向顺式作用的印记中心（IC），位于上游的theNurf/Snrpn基因协调。IC如何调节整个结构域的基因表达的分子机制仍然是部分理解的。在这里，我们分析了印迹基因表达和DNA甲基化之间的关系，在小鼠染色体7 C使用DNA甲基转移酶1（DNMT 1）-null突变胚胎携带Dnmt 1 ps等位基因，这表明全球丢失的DNA甲基化和胚胎致死性。在DNMT 1-null胚胎在胚胎的第9.5天，父系表达的基因是双等位基因表达。亚硫酸氢盐DNA甲基化分析显示，在基因的启动子区域中，母体等位基因上的甲基化丢失。这些结果表明，DNMT 1是必要的单等位基因的印记基因在染色体7 C域的表达，表明在第二个差异甲基化区域（DMR），这是在发展过程中获得的DNA甲基化主要用于控制印记基因的表达从母体等位基因在小鼠染色体7 C。
The mouse chromosome 7C, orthologous to the human 15q11–q13 has an imprinted domain, where most of the genes are expressed only from the paternal allele. The imprinted domain contains paternally expressed genes,Snurf/Snrpn,Ndn,Magel2,Mkrn3, andFrat3, C/D-box small nucleolar RNAs (snoRNAs), and the maternally expressed gene,Ube3a. Imprinted expression in this large (approximately 3–4 Mb) domain is coordinated by a bipartite cis-acting imprinting center (IC), located upstream of theSnurf/Snrpngene. The molecular mechanism how IC regulates gene expression of the whole domain remains partially understood. Here we analyzed the relationship between imprinted gene expression and DNA methylation in the mouse chromosome 7C using DNA methyltransferase 1 (DNMT1)-null mutant embryos carryingDnmt1psalleles, which show global loss of DNA methylation and embryonic lethality. In the DNMT1-null embryos at embryonic day 9.5, the paternally expressed genes were biallelically expressed. Bisulfite DNA methylation analysis revealed loss of methylation on the maternal allele in the promoter regions of the genes. These results demonstrate that DNMT1 is necessary for monoallelic expression of the imprinted genes in the chromosome 7C domain, suggesting that DNA methylation in the secondary differentially methylated regions (DMRs), which are acquired during development serves primarily to control the imprinted expression from the maternal allele in the mouse chromosome 7C.