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Evidence for de novo imprinted X-chromosome inactivation independent of meiotic inactivation in mice

机译:与小鼠减数分裂灭活无关的从头印迹X染色体灭活的证据

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In mammals, one of the two X chromosomes is inactivated in females to enable dosage compensation for X-linked gene products. In rodents and marsupials, only the X chromosome of paternal origin (Xp) is silenced during early embryogenesis. This could be due to a carry-over effect of the X chromosome's passage through the male germ line, where it becomes transiently silenced together with the Y chromosome, during meiotic sex chromosome inactivation (MSCI). Here we show that Xist (X inactive specific transcript) transgenes, located on autosomes, do not undergo MSCI in the male germ line of mice and yet can induce imprinted cis-inactivation when paternally inherited, with identical kinetics to the Xp chromosome. This suggests that MSCI is not necessary for imprinted X-chromosome inactivation in mice. We also show that the Xp is transcribed, like autosomes, at zygotic gene activation rather than being 'pre-inactivated'. We propose that expression of the paternal Xist gene at zygotic gene activation is sufficient to trigger cis-inactivation of the X chromosome, or of an autosome carrying a Xist transgene.
机译:在哺乳动物中,雌性使两个X染色体之一失活,以实现X连锁基因产物的剂量补偿。在啮齿动物和有袋动物中,在早期胚胎发生过程中只有父系起源的X染色体(Xp)被沉默。这可能是由于减数分裂性染色体失活(MSCI)过程中X染色体穿过雄性种系的残留效应,在这里它与Y染色体一起被暂时沉默。在这里,我们显示位于常染色体上的Xist(X失活的特定转录本)转基因在小鼠的雄性种系中不经历MSCI,但在父系继承时可以诱导印迹的顺式失活,其动力学与Xp染色体相同。这表明MSCI对于小鼠印迹X染色体灭活不是必需的。我们还显示,Xp与常染色体一样在合子基因激活时被转录,而不是被“预灭活”。我们提出,在合子基因激活时,父系Xist基因的表达足以触发X染色体或带有Xist转基因的常染色体的顺式失活。

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