Krumlauf R, Chapman V M, Hammer R E, Brinster R, Tilghman S M
Nature. 1986;319(6050):224-6. doi: 10.1038/319224a0.
During development of the female mouse embryo, one of the two X chromosomes is inactivated in a random manner in most cell lineages. However, in the extraembryonic trophectoderm and primary endoderm lineages there is preferential inactivation of the paternally derived X chromosome. The inactivated X chromosomes of the extraembryonic and somatic tissues appear equally inactive at the level of the expression of X-linked genes. However, there are differences in the timing of their replication and the extent of DNA modification as determined by gene transfer. The identification of transgenic animals carrying X-linked modified alpha-fetoprotein (AFP) genes allowed us to examine whether the inactivation process extends to an autosomal gene which is normally expressed at high levels in specific extraembryonic and somatic cells, and if so, whether the inactivation process is different in these two tissues. Our results demonstrate that the X-linked AFP genes were expressed on the inactive X chromosome in the visceral endoderm of the yolk sac but not in fetal liver. Thus, the transcriptional activity of the AFP minigene on the inactive X chromosome is dependent on the tissue in which it resides, and most probably reflects differences in the nature of the maintenance of the inactive state of the extraembryonic and embryonic X chromosomes.
在雌性小鼠胚胎发育过程中，两条X染色体中的一条在大多数细胞谱系中以随机方式失活。然而，在胚外滋养外胚层和原始内胚层谱系中，父源X染色体优先失活。在X连锁基因表达水平上，胚外组织和体细胞组织中失活的X染色体看起来同样无活性。然而，通过基因转移确定，它们在复制时间和DNA修饰程度上存在差异。携带X连锁修饰甲胎蛋白（AFP）基因的转基因动物的鉴定，使我们能够研究失活过程是否延伸至一个常染色体基因，该基因通常在特定的胚外和体细胞中高水平表达；如果是这样，在这两种组织中失活过程是否不同。我们的结果表明，X连锁的AFP基因在卵黄囊内胚层的失活X染色体上表达，但在胎儿肝脏中不表达。因此，失活X染色体上AFP小基因的转录活性取决于其所在的组织，很可能反映了胚外和胚胎X染色体失活状态维持性质的差异。
