Monk M, Grant M
MRC Mammalian Development Unit, London, UK.
Dev Suppl. 1990:55-62.
Non-random X-chromosome inactivation in mammals was one of the first observed examples of differential expression dependent on the gamete of origin of the genetic material. The paternally-inherited X chromosome is preferentially inactive in all cells of female marsupials and in the extra-embryonic tissues of developing female rodents. Some form of parental imprinting during male and female gametogenesis must provide a recognition signal that determines the nonrandomness of X-inactivation but its nature is thus far unknown. In the mouse, the imprint distinguishing the X chromosomes in the extra-embryonic tissues must be erased early in development since X-inactivation is random in the embryonic cells. Random X-chromosome inactivation leads to cellular mosaicism in expression and differential methylation of active and inactive X-linked genes. Transgene imprinting shares many features with X-inactivation, including differential DNA methylation. In this paper we consider when methylation differences in early development affecting X-chromosome activity and imprinting are established. There are processes of methylation and demethylation occurring in early development, as well as changes in the activity of the DNA methylase itself. Methylation of a specific CpG site associated with activity of the X-linked PGK-1 gene has been studied. This site is already methylated on the inactive X chromosome by 6.5 days' gestation, close to the time of X-inactivation. However, differential methylation of this site is not the primary imprint marking the paternal X chromosome for preferential inactivation in the extra-embryonic membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
哺乳动物中X染色体的非随机失活是最早观察到的依赖于遗传物质起源配子的差异表达实例之一。在雌性有袋动物的所有细胞以及发育中的雌性啮齿动物的胚外组织中，父本遗传的X染色体优先失活。在雄性和雌性配子发生过程中，某种形式的亲本印记必定提供了一种识别信号，该信号决定了X染色体失活的非随机性，但其本质至今仍不清楚。在小鼠中，区分胚外组织中X染色体的印记必须在发育早期被消除，因为X染色体失活在胚胎细胞中是随机的。随机的X染色体失活导致细胞在表达上的镶嵌现象以及活性和非活性X连锁基因的差异甲基化。转基因印记与X染色体失活有许多共同特征，包括DNA甲基化差异。在本文中，我们探讨了影响X染色体活性和印记的早期发育甲基化差异是何时建立的。早期发育过程中存在甲基化和去甲基化过程，以及DNA甲基化酶本身活性的变化。已经对与X连锁的磷酸甘油酸激酶-1（PGK-1）基因活性相关的特定CpG位点的甲基化进行了研究。在妊娠6.5天时，该位点在失活的X染色体上已经发生甲基化，接近X染色体失活的时间。然而，该位点的差异甲基化并不是在胚外膜中标记父本X染色体以便优先失活的主要印记。（摘要截短于250字）
