9月5日,，國際著名期刊《自然》雜志在線發(fā)表了中國科學(xué)院上海生命科學(xué)研究院生物化學(xué)與細胞生物學(xué)研究所徐國良課題組和李勁松課題組關(guān)于卵細胞重編程機制的最新研究成果,，首次闡明了自然受精和克隆過程中卵細胞重編程的機制,，使人們對早期胚胎如何獲得正常的發(fā)育能力有了更清晰的認識,。
精子和卵細胞融合為一個受精卵的過程,，是動物個體發(fā)育的起點,。為了形成一個具有發(fā)育全能型的早期胚胎,，卵細胞需要對精子基因組進行一系列的重編,。其中,，最為重要的一項就是基因組DNA上胞嘧啶堿基的去甲基化。人們并不清楚這種化學(xué)修飾的改變是如何實現(xiàn)的,，也不知道它為什么要發(fā)生,。
中國科學(xué)院上海生命科學(xué)研究院的該研究工作發(fā)現(xiàn)，來自卵細胞的一個叫做“Tet3”的母源蛋白可以氧化精子基因組DNA,，并進一步調(diào)控父源基因的表達,，以支持早期胚胎的正常發(fā)育。卵細胞去除“Tet3”氧化酶的母鼠生育力顯著下降,，大部分胚胎在妊娠期發(fā)生了退化,，被母體吸收。此外,，在動物克隆過程中,，“Tet3”也同樣發(fā)揮著重要的作用。這項研究為開發(fā)女性不孕不育癥的治療手段提供了新的理論依據(jù)和參考,，也為提高動物克隆效率帶來了新的希望,。(生物谷 Bioon.com)
doi:10.1038/nature10443
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PMID:
The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
Tian-Peng Gu; Fan Guo; Hui Yang; Hai-Ping Wu; Gui-Fang Xu; Wei Liu; Zhi-Guo Xie; Linyu Shi; Xinyi He; Seung-gi Jin; Khursheed Iqbal; Yujiang Geno Shi; Zixin Deng; Piroska E. Szabó; Gerd P. Pfeifer; Jinsong Li; Guo-Liang Xu
Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization1. The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis2, 3. The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear4. Here we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC). Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched specifically in the male pronucleus. In Tet3-deficient zygotes from conditional knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation process of the paternal Oct4 and Nanog genes and delays the subsequent activation of a paternally derived Oct4 transgene in early embryos. Female mice depleted of Tet3 in the germ line show severely reduced fecundity and their heterozygous mutant offspring lacking maternal Tet3 suffer an increased incidence of developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA following natural fertilization and may also contribute to somatic cell nuclear reprogramming during animal cloning.
