nature20121220-9

来自哈佛大学医学院的张毅研究组与加州大学圣地亚哥分校合作,发现了Tet蛋白的又一新功能―Tet1能通过调控减数分裂基因表达来操控减数分裂过程。

-2012年12月20日《自然》


中文翻译


【题目】Tet1通过调控减数分裂基因表达控制减数分裂

【译文】减数分裂是生殖细胞特有的细胞分裂过程,能通过单倍体配子实现有性繁殖。在减数分裂启动之前,小鼠的原始生殖细胞会发生一系列的表观遗传重编程步骤,比如CpG富集的DNA上,5mC位置会出现DNA甲基化的全面清除。虽然目前科学家们已经了解了减数分裂过程中关键的几个表观遗传调控因子,如DNMT3L,组蛋白甲基化转移酶G9A和Prdm9,但对于这一过程中基因的表达受到什么调控,以及如何控制正常减数分裂进行,知之甚少。在小鼠中采用功能丧失性诱变方法,本研究发现Tet1这一5mC特定双加氧酶,在小鼠卵母细胞减数分裂调控中扮演了重要角色。Tet1缺乏会显著减少雌性生殖细胞数量和生育率。单价染色体和未分解的DNA双链断裂也在Tet1缺陷的卵母细胞中观察到。小鼠如果缺乏Tet1,虽然并不会对原始生殖细胞的全基因组范围内去甲基化造成极大的影响,但是却会导致DNA去甲基化出现缺陷,并且降低一组减数分裂基因的表达。本研究因此揭示出了Tet1在减数分裂,以及雌性生殖细胞减数分裂基因活性调控中的重要作用。

英文原稿


[Title]: Tet1 controls meiosis by regulating meiotic gene expression

[Authors]:Shinpei Yamaguchi,1, 2, 3, 6 Kwonho Hong,1, 2, 3, 6 Rui Liu,4, 6 Li Shen,1, 2, 3 Azusa Inoue,1, 2, 3 Dinh Diep,4 Kun Zhang4 & Yi Zhang1, 2, 3, 5

[Abstract]:Meiosis is a germ-cell-specific cell division process through which haploid gametes are produced for sexual reproduction. Before the initiation of meiosis, mouse primordial germ cells undergo a series of epigenetic reprogramming steps, including the global erasure of DNA methylation at the 5-position of cytosine (5mC) in CpG-rich DNA. Although several epigenetic regulators, such as Dnmt3land the histone methyltransferases G9aand Prdm9, have been reported to be crucial for meiosis, little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. Using a loss-of-function approach in mice, here we show that the 5mC-specific dioxygenase Tet1 has an important role in regulating meiosis in mouse oocytes. Tet1 deficiency significantly reduces female germ-cell numbers and fertility. Univalent chromosomes and unresolved DNA double-strand breaks are also observed in Tet1-deficient oocytes. Tet1 deficiency does not greatly affect the genome-wide demethylation that takes place in primordial germ cells, but leads to defective DNA demethylation and decreased expression of a subset of meiotic genes. Our study thus establishes a function for Tet1 inmeiosis and meiotic gene activation in female germ cells.

原文地址

http://www.nature.com/nature/journal/v492/n7429/full/nature11709.html

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