Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos
Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos
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DOI：
10.1038/nature02222
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发表时间：
2003-12-18
期刊：
影响因子：
64.8
通讯作者：
Lee, JT
中科院分区：
文献类型：
--
作者：
Huynh, KD;Lee, JT
在哺乳动物中，剂量补偿通过转录沉默XX胚胎中的一条X染色体来确保雄性(XY)和雌性(XX)X染色体的平等表达(1)。在流行的观点中，XX受精卵继承了两条活跃的X染色体，分别来自母亲和父亲，X染色体失活直到植入后才发生(2-6)。在这里，我们在老鼠身上报告了相反的证据。我们发现一条X染色体在合子基因激活(2-细胞期)时已经沉默。这条X染色体起源于父系，并表现出沉默的梯度。靠近X-失活中心的基因表现出最大程度的失活，而更远端的基因表现出可变的失活，并可以部分逃脱沉默。植入后，胚胎外组织中的印迹沉默在逐个基因的基础上变得全球化和更加完整。这些结果表明，XX胚胎实际上是沿着X染色体的大部分在受孕时得到剂量补偿的。我们认为印记X失活是来自父系生殖系的一条预先失活的X染色体的遗传。
In mammals, dosage compensation ensures equal X-chromosome expression between males (XY) and females (XX) by transcriptionally silencing one X chromosome in XX embryos(1). In the prevailing view, the XX zygote inherits two active X chromosomes, one each from the mother and father, and X inactivation does not occur until after implantation(2-6). Here, we report evidence to the contrary in mice. We find that one X chromosome is already silent at zygotic gene activation (2-cell stage). This X chromosome is paternal in origin and exhibits a gradient of silencing. Genes close to the X-inactivation centre show the greatest degree of inactivation, whereas more distal genes show variable inactivation and can partially escape silencing. After implantation, imprinted silencing in extraembryonic tissues becomes globalized and more complete on a gene-by-gene basis. These results argue that the XX embryo is in fact dosage compensated at conception along much of the X chromosome. We propose that imprinted X inactivation results from inheritance of a pre-inactivated X chromosome from the paternal germ line.