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Nature:基因组印记被Tet1抹掉

  1. Tet1
  2. 印记
  3. 基因组
  4. 抹掉

来源:Nature中文网 2013-12-19 11:16

由等位基因特异性DNA甲基化介导的基因组印记,在发生在原始生殖细胞中的全基因组重新编程过程中一定要被抹掉。

由等位基因特异性DNA甲基化介导的基因组印记,在发生在原始生殖细胞中的全基因组重新编程过程中一定要被抹掉。

在这项研究中,Yi Zhang及同事确定了“甲基胞嘧啶加双氧酶”Tet1在活体中抹掉基因组印记中所起的一个重要作用。父方Tet1被敲除的小鼠会产生有印记缺陷及相关的生长和发育缺陷的后代,这会导致早期胚胎死亡。

对重新编程的原始生殖细胞中的DNA甲基化动态所做的分析表明,Tet1在重新编程过程的晚期、在第二波的DNA去甲基化中是必需的。(生物谷Bioon.com)

生物谷推荐的英文摘要

Nature          doi:10.1038/nature12805

Role of Tet1 in erasure of genomic imprinting

Shinpei Yamaguchi,  Li Shen,  Yuting Liu,  Damian Sendler  & Yi Zhang

Genomic imprinting is an allele-specific gene expression system that is important for mammalian development and function1. The molecular basis of genomic imprinting is allele-specific DNA methylation1, 2. Although it is well known that the de novo DNA methyltransferases Dnmt3a and Dnmt3b are responsible for the establishment of genomic imprinting3, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains unclear. Tet1 is one of the ten-eleven translocation family proteins, which have the capacity to oxidize 5-methylcytosine (5mC)4, 5, 6, specifically expressed in reprogramming PGCs7. Here we report that Tet1 has a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1 knockout males and wild-Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal loss of Tet1 function. Genome-wide DNA methylation analysis of embryonic day 13.5 PGCs and sperm of Tet1 knockout mice revealed hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Analysis of the DNA methylation dynamics in reprogramming PGCs indicates that Tet1 functions to wipe out remaining methylation, including imprinted genes, at the late reprogramming stage. Furthermore, we provide evidence supporting the role of Tet1 in the erasure of paternal imprints in the female germ line. Thus, our study establishes a critical function of Tet1 in the erasure of genomic imprinting.

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