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

In mammals, one of the two X chromosomes is inactivated in females to enable dosage compensation for X-linked gene products1. 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)2. 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’3. 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.