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- 积分
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- 威望
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原文摘要：
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The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes
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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.
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Derivation of haploid embryonic stem cells from mouse embryos
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Most animals are diploid, but haploid-only and male-haploid (such as honeybee and ant) species have been described1. The diploid genomes of complex organisms limit genetic approaches in biomedical model species such as mice. To overcome this problem, experimental induction of haploidy has been used in fish2, 3. Haploid development in zebrafish has been applied for genetic screening2. Recently, haploid pluripotent cell lines from medaka fish (Oryzias latipes) have also been established3. In contrast, haploidy seems less compatible with development in mammals4, 5. Although haploid cells have been observed in egg cylinder stage parthenogenetic mouse embryos6, most cells in surviving embryos become diploid. Here we describe haploid mouse embryonic stem cells and show their application in forward genetic screening.% w& q& n9 p2 ?) P
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发表于 2011-9-9 09:15
发表于 2011-9-9 10:19
发表于 2011-9-10 14:58
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