iPS 李劲松The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.pdfVIP

LETTER doi:10.1038/nature10443 The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes 1 1 2 1 1 1 1 2 3 Tian-Peng Gu *, Fan Guo *, Hui Yang *, Hai-Ping Wu {, Gui-Fang Xu , Wei Liu , Zhi-Guo Xie , Linyu Shi , Xinyi He , 4 5 6 3 ´5 4 2 1 Seung-gi Jin , Khursheed Iqbal , Yujiang Geno Shi , Zixin Deng , Piroska E. Szabo , Gerd P. Pfeifer , Jinsong Li Guo-Liang Xu Sperm and eggs carry distinctive epigenetic modifications that are To study the biological function of Tet3 in mouse, we generated a adjusted by reprogramming after fertilization1. The paternal conditional knockout allele abolishing its catalytic activity (Supplemen- genome in a zygote undergoes active DNA demethylation before tary Fig. 6a). Because homozygous mutation led to neonatal lethality, the first mitosis2,3. The biological significance and mechanisms of we achieved germ-line-specific deletion of Tet3 from primordial germ 4 f/ 2 this paternal epigenome remodelling have remained unclear . Here cells (PGCs) in [Tet3 , TNAP-Cre] conditional knockout (CKO) we report that, within mouse zygotes, oxidation of 5-methylcytosine mice. (5mC) occurs on the paternal genome, changing 5mC into 5- Female CKO mice were normal in growth