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The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
文献类型:期刊论文
作者 | Gu, TP; Guo, F; Yang, H; Wu, HP; Xu, GF; Liu, W; Xie, ZG; Shi, LY; He, XY; Jin, SG |
刊名 | NATURE
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出版日期 | 2011 |
卷号 | 477期号:7366页码:606-U136 |
通讯作者 | Li, JS (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,jsli@sibs.ac.cn ; glxu@sibs.ac.cn |
英文摘要 | Sperm and eggs carry distinctive epigenetic modifications that are adjusted by reprogramming after fertilization(1). The paternal genome in a zygote undergoes active DNA demethylation before the first mitosis(2,3). The biological significance and mechanisms of this paternal epigenome remodelling have remained unclear(4). 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. |
学科主题 | Science & Technology - Other Topics |
类目[WOS] | Multidisciplinary Sciences |
关键词[WOS] | PRIMORDIAL GERM-CELLS ; EMBRYONIC STEM-CELLS ; PATERNAL GENOME ; CRE RECOMBINASE ; MOUSE ZYGOTES ; 5-HYDROXYMETHYLCYTOSINE ; DEMETHYLATION ; GENES ; 5-METHYLCYTOSINE ; METHYLATION |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000295320900043 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/896] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Gu, TP,Guo, F,Yang, H,et al. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes[J]. NATURE,2011,477(7366):606-U136. |
APA | Gu, TP.,Guo, F.,Yang, H.,Wu, HP.,Xu, GF.,...&Xu, GL.(2011).The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.NATURE,477(7366),606-U136. |
MLA | Gu, TP,et al."The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes".NATURE 477.7366(2011):606-U136. |
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