DNA的5-甲基胞嘧啶(5-methylcytosine,5mC )修饰在细胞的分化和发育过程中起着重要的调节作用。在双加氧酶Tet家族成员的作用下5mC修饰可以羟化成5hmC(5-hydroxymethylcytosine)修饰。值得注意的是,基因组中5mC与5hmC之间的平衡与很多生物学事件有关,比如细胞的多能性与谱系决定。
在小鼠胚胎早期发育过程中,父源基因需要去甲基化,而母源基因因受到某种机制的保护不发生去甲基化。
本文研究者之前的研究表明,母源因子PGC7在维持早起胚胎甲基化中是必要的,它能够防止母源基因5mC向5mhC的转变。在本文中研究者证明了PGC7能够结合母源染色体上H3K9me2位点,从而防止Tet3介导的5mC向5mhC转化。(生物谷 Bioon.com )
doi:10.1038/nature11093
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PGC7 binds histone H3K9me2 to protect against conversion of 5mC to 5hmC in early embryos
Toshinobu Nakamura, Yu-Jung Liu, Hiroyuki Nakashima, Hiroki Umehara, Kimiko Inoue, Shogo Matoba, Makoto Tachibana, Atsuo Ogura, Yoichi Shinkai & Toru Nakano
The modification of DNA by 5-methylcytosine (5mC) has essential roles in cell differentiation and development through epigenetic gene regulation. 5mC can be converted to another modified base, 5-hydroxymethylcytosine (5hmC), by the tet methylcytosine dioxygenase (Tet) family of enzymes. Notably, the balance between 5hmC and 5mC in the genome is linked with cell-differentiation processes such as pluripotency and lineage commitment. We have previously reported that the maternal factor PGC7 (also known as Dppa3, Stella) is required for the maintenance of DNA methylation in early embryogenesis, and protects 5mC from conversion to 5hmC in the maternal genome. Here we show that PGC7 protects 5mC from Tet3-mediated conversion to 5hmC by binding to maternal chromatin containing dimethylated histone H3 lysine 9 (H3K9me2) in mice. In addition, imprinted loci that are marked with H3K9me2 in mature sperm are protected by PGC7 binding in early embryogenesis. This type of regulatory mechanism could be involved in DNA modifications in somatic cells as well as in early embryos.