PGC7/Stella protects against DNA demethylation in early embryogenesis
PGC7/Stella protects against DNA demethylation in early embryogenesis
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DOI：
10.1038/ncb1519
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发表时间：
2007-01-01
影响因子：
21.3
通讯作者：
Nakano, Toru
中科院分区：
文献类型：
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作者：
Nakamura, Toshinobu;Arai, Yoshikazu;Nakano, Toru
DNA甲基化是表观遗传基因调控(1，2)的重要手段，必须仔细控制，作为正常早期胚胎发育的先决条件。虽然整体去甲基化在受精后不久就发生了，但它并不均匀地分布在整个基因组中。基因组印记和亲本基因组之间的表观遗传不对称，即受精后母体基因组的延迟去甲基化(3-6)，是DNA甲基化功能重要性的明显例子。在这里，我们展示了PGC7/Stella，一种对早期发育必不可少的母性因子，保护了几个印记基因座的DNA甲基化状态和表观遗传不对称性。在确定PGC7/Stella与RAN结合蛋白5(RanBP5；一种核运输穿梭蛋白)结合后，使用这两种蛋白的突变版本来确切地检测PGC7/Stella在细胞内发挥作用的时间和位置。很可能PGC7/Stella只有在定位到细胞核后才能保护母体基因组免受去甲基化的影响，在那里它维持着几个印记基因的甲基化。这些结果表明，在受精后的表观遗传重编程过程中，PGC7/Stella对于维持甲基化是必不可少的。
DNA methylation is an important means of epigenetic gene regulation(1,2) and must be carefully controlled as a prerequisite for normal early embryogenesis. Although global demethylation occurs soon after fertilization, it is not evenly distributed throughout the genome. Genomic imprinting and epigenetic asymmetry between parental genomes, that is, delayed demethylation of the maternal genome after fertilization(3-6), are clear examples of the functional importance of DNA methylation. Here, we show that PGC7/Stella, a maternal factor essential for early development, protects the DNA methylation state of several imprinted loci and epigenetic asymmetry. After determining that PGC7/Stella binds to Ran binding protein 5 (RanBP5; a nuclear transport shuttle protein), mutant versions of the two proteins were used to examine exactly when and where PGC7/Stella functions within the cell. It is likely that PGC7/Stella protects the maternal genome from demethylation only after localizing to the nucleus, where it maintains the methylation of several imprinted genes. These results demonstrate that PGC7/Stella is indispensable for the maintenance of methylation involved in epigenetic reprogramming after fertilization.