Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice
Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice
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DOI：
10.1073/pnas.0810683106
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发表时间：
2009-03-31
影响因子：
11.1
通讯作者：
Heard, Edith
中科院分区：
文献类型：
--
作者：
Patrat, Catherine;Okamoto, Ikuhiro;Heard, Edith
在哺乳动物中，X染色体剂量补偿是通过使雌性两条X染色体中的一条失活来实现的。在小鼠中，X失活最初是印记的，父亲的X(XP)染色体在植入前发育期间发生失活。一种理论认为，XP在雌性胚胎中是预失活的，因为它以前在雄性生殖系减数分裂期间保持沉默。受精后XP的活跃程度以及X连锁基因沉默的确切时间一直是争论的主题。我们进行了系统的单细胞转录分析，以检测一组X连锁基因在小鼠早期植入前发育过程中XP染色体的活性。我们发现XP在合子基因激活时是完全活跃的，而不是被预灭活，从4-细胞阶段开始沉默。然而，令人惊讶的是，不同基因之间的X失活模式是不同的。有些基因座表现出较早的X失活(4-8细胞期)，有些基因座表现出极晚的X失活(胚泡后阶段)，而另一些基因座则从未完全失活。因此，我们表明，一些X染色体区域的沉默发生在通常的时间窗口之外，并且从X染色体失活中逃脱可能是高度世系特有的。这些结果表明，印记X在小鼠中的失活远没有之前认为的那么一致，并突显了哺乳动物早期发育过程中剂量补偿过程的表观遗传多样性。
In mammals, X-chromosome dosage compensation is achieved by inactivating one of the two X chromosomes in females. In mice, X inactivation is initially imprinted, with inactivation of the paternal X (Xp) chromosome occurring during preimplantation development. One theory is that the Xp is preinactivated in female embryos, because of its previous silence during meiosis in the male germ line. The extent to which the Xp is active after fertilization and the exact time of onset of X-linked gene silencing have been the subject of debate. We performed a systematic, single-cell transcriptional analysis to examine the activity of the Xp chromosome for a panel of X-linked genes throughout early preimplantation development in the mouse. Rather than being preinactivated, we found the Xp to be fully active at the time of zygotic gene activation, with silencing beginning from the 4-cell stage onward. X-inactivation patterns were, however, surprisingly diverse between genes. Some loci showed early onset (4-8-cell stage) of X inactivation, and some showed extremely late onset (postblastocyst stage), whereas others were never fully inactivated. Thus, we show that silencing of some X-chromosomal regions occurs outside of the usual time window and that escape from X inactivation can be highly lineage specific. These results reveal that imprinted X inactivation in mice is far less concerted than previously thought and highlight the epigenetic diversity underlying the dosage compensation process during early mammalian development.