X chromosome reactivation initiates in nascent primordial germ cells in mice.
X chromosome reactivation initiates in nascent primordial germ cells in mice.
复制标题
X染色体重新激活在小鼠的新生原始生殖细胞中启动。
DOI：
10.1371/journal.pgen.0030116
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发表时间：
2007-07
期刊：
影响因子：
4.5
通讯作者：
Abe, Kuniya
中科院分区：
文献类型：
--
作者：
Sugimoto, Michihiko;Abe, Kuniya
在原始生殖细胞(PGC)发育期间，以X染色体重新激活和基因组印记擦除为代表的表观遗传重编程事件是已知的。虽然没有给出确切的时间，但X的重新激活被认为发生在减数分裂开始之前的一小段时间内。在这里，我们发现Xist表达的停止在新生的原生殖细胞中开始，而一些X连锁基因的重新表达在新形成的原生殖细胞中开始。在E14.5PGC中，X再激活过程没有完成，这表明发育中的PGC中的X重新激活发生的时间较长。这些结果将重新激活的时间设置得比之前认为的要早得多，并表明X的重新激活可能涉及缓慢的被动步骤。X染色体失活是补偿哺乳动物XY雄性和XX雌性基因剂量差异的一种机制。在胚胎发育的早期，每个雌性细胞中的两条X染色体中的一条被失活，而失活的X染色体通过体细胞的分裂稳定地遗传。虽然没有给出确切的时间，但已知在生殖细胞发育过程中，不活跃的X染色体会重新激活。一般认为，X染色体活性的动态变化与哺乳动物发育过程中发生的主要基因组重编程事件密切相关。因此，阐明X染色体再激活动力学对于理解X染色体失活/再激活过程以及表观遗传重编程过程具有重要意义。在这里，我们研究了在雌性小鼠生殖细胞发育过程中X重新激活的时间。与之前的建议相反，X的重新激活已经在雌性小鼠的新生原始生殖细胞中开始，并逐渐进行，需要一段较长的时间。在重新激活的过程中，生殖细胞的X染色体的活动状态似乎因细胞和基因的不同而不同。这些结果表明，X的重新激活与生殖细胞的形成相一致，并表明这涉及缓慢的被动步骤。
During primordial germ cell (PGC) development, epigenetic reprogramming events represented by X chromosome reactivation and erasure of genomic imprinting are known to occur. Although precise timing is not given, X reactivation is thought to take place over a short period of time just before initiation of meiosis. Here, we show that the cessation of Xist expression commences in nascent PGCs, and re-expression of some X-linked genes begins in newly formed PGCs. The X reactivation process was not complete in E14.5 PGCs, indicating that X reactivation in developing PGCs occurs over a prolonged period. These results set the reactivation timing much earlier than previously thought and suggest that X reactivation may involve slow passive steps. X chromosome inactivation is a mechanism to compensate gene dosage difference between XY males and XX females in mammals. During early embryogenesis, one of two X chromosomes in every female cell is inactivated, and the inactive X chromosome is stably inherited through cell divisions of somatic cells. Although precise timing is not given, the inactive X chromosome is known to be reactivated during germ cell development. It is generally believed that the dynamics of X chromosome activity is tightly correlated with major genomic reprogramming events occurring during mammalian development. Therefore, elucidation of the X reactivation kinetics is important for understanding the mechanism of X chromosome inactivation/reactivation processes and the epigenetic reprogramming processes as well. Here we investigated when X reactivation is initiated during development of female mouse germ cells. Contrary to the previous suggestions, X reactivation already begins in nascent primordial germ cells in female mice and proceeds gradually requiring a prolonged period. The activity status of the X chromosomes of germ cells appears to vary from cell-to-cell and from gene-to-gene during the reactivation processes. These results indicate that the X reactivation coincides with the formation of germ cells and suggest that this involves slow passive steps.
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