The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes

	The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
	Gu, TP; Guo, F; Yang, H; Wu, HP; Xu, GF; Liu, W; Xie, ZG; Shi, LY; He, XY; Jin, SG
刊名	NATURE
	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
内容类型	期刊论文
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.