GSE is a maternal factor involved in active DNA demethylation in zygotes.
GSE is a maternal factor involved in active DNA demethylation in zygotes.
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DOI：
10.1371/journal.pone.0060205
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Matsumoto K
中科院分区：
文献类型：
--
作者：
Hatanaka Y;Shimizu N;Nishikawa S;Tokoro M;Shin SW;Nishihara T;Amano T;Anzai M;Kato H;Mitani T;Hosoi Y;Kishigami S;Matsumoto K
受精后，精子和卵母细胞基因组经历广泛的表观遗传重编程，形成全能合子。早期胚胎发育过程中表观遗传学的动态变化主要涉及DNA甲基化和去甲基化。我们以前已经确定Gse（性腺特异性表达基因）在生殖细胞和早期胚胎中特异性表达。其编码的蛋白质GSE主要定位于从受精卵到囊胚阶段的细胞核中，这表明在早期胚胎发育期间发生的表观遗传变化中可能起作用。在这里，我们报告的参与GSE在表观遗传重编程的父亲基因组在小鼠受精卵发育。从原核阶段2（PN 2）向前观察到GSE与父本染色质的优先结合。用反义RNA敲低卵母细胞中的GSE对植入前胚胎的第一和第二细胞周期没有明显的影响，但引起父本原核中5-甲基胞嘧啶（5 mC）的丢失和5-羟甲基胞嘧啶（5 hmC）的积累显著减少。此外，在原核中期（PN 3 -4）GSE敲除合子中，LINE 1转座元件、Lemd 1、Nanog和Oct 4基因上游调控区（也称为Pou 5 f1）的CpG位点的DNA甲基化水平明显增加，但印迹H19差异甲基化区域不受影响。重要的是，5 mC和5 hmC的DNA免疫沉淀也表明，合子中GSE的敲低导致LINE 1上5 mC向5 hmC的转化显著减少。因此，我们的研究结果表明，在受精卵中，母体GSE介导主动DNA去甲基化的重要作用。
After fertilization, the sperm and oocyte genomes undergo extensive epigenetic reprogramming to form a totipotent zygote. The dynamic epigenetic changes during early embryo development primarily involve DNA methylation and demethylation. We have previously identified Gse (gonad-specific expression gene) to be expressed specifically in germ cells and early embryos. Its encoded protein GSE is predominantly localized in the nuclei of cells from the zygote to blastocyst stages, suggesting possible roles in the epigenetic changes occurring during early embryo development. Here, we report the involvement of GSE in epigenetic reprogramming of the paternal genome during mouse zygote development. Preferential binding of GSE to the paternal chromatin was observed from pronuclear stage 2 (PN2) onward. A knockdown of GSE by antisense RNA in oocytes produced no apparent effect on the first and second cell cycles in preimplantation embryos, but caused a significant reduction in the loss of 5-methylcytosine (5mC) and the accumulation of 5-hydroxymethylcytosine (5hmC) in the paternal pronucleus. Furthermore, DNA methylation levels in CpG sites of LINE1 transposable elements, Lemd1, Nanog and the upstream regulatory region of the Oct4 (also known as Pou5f1) gene were clearly increased in GSE-knockdown zygotes at mid-pronuclear stages (PN3-4), but the imprinted H19-differential methylated region was not affected. Importantly, DNA immunoprecipitation of 5mC and 5hmC also indicates that knockdown of GSE in zygotes resulted in a significant reduction of the conversion of 5mC to 5hmC on LINE1. Therefore, our results suggest an important role of maternal GSE for mediating active DNA demethylation in the zygote.
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