9月5日，国际著名期刊《自然》杂志在线发表了中国科学院上海生命科学研究院生物化学与细胞生物学研究所徐国良课题组和李劲松课题组关于卵细胞重编程机制的最新研究成果，首次阐明了自然受精和克隆过程中卵细胞重编程的机制，使人们对早期胚胎如何获得正常的发育能力有了更清晰的认识。
精子和卵细胞融合为一个受精卵的过程，是动物个体发育的起点。为了形成一个具有发育全能型的早期胚胎，卵细胞需要对精子基因组进行一系列的重编。其中，最为重要的一项就是基因组DNA上胞嘧啶碱基的去甲基化。人们并不清楚这种化学修饰的改变是如何实现的，也不知道它为什么要发生。
中国科学院上海生命科学研究院的该研究工作发现，来自卵细胞的一个叫做“Tet3”的母源蛋白可以氧化精子基因组DNA，并进一步调控父源基因的表达，以支持早期胚胎的正常发育。卵细胞去除“Tet3”氧化酶的母鼠生育力显著下降，大部分胚胎在妊娠期发生了退化，被母体吸收。此外，在动物克隆过程中，“Tet3”也同样发挥着重要的作用。这项研究为开发女性不孕不育症的治疗手段提供了新的理论依据和参考，也为提高动物克隆效率带来了新的希望。(生物谷 Bioon.com)
doi:10.1038/nature10443
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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.
