Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation

In mammals, X-chromosome inactivation (XCl) ensures equal expression of X-l inked genes in XX and XY individuals by transcriptionally silencing one X-c hromosome in female cells. In this review, we discuss an imprinted form of X-inactivation in which the paternal X (Xp) is preferentially silenced. Bel ieved to be the ancestral mechanism of dosage compensation in mammals, impr inted X-inactivation can still be observed in modern-day marsupials and in the extraembryonic tissues of some eutherians such as the mouse. Recent exp eriments have addressed the nature of the gametic imprint and focused on th e regulatory interaction between the noncoding RNA gene, Xist, and its anti sense partner, Tsix. Our review of the literature has inspired an unconvent ional view of imprinted XCl in mice. First, the evidence strongly argues th at imprinted Cl is inabsolute, so that a stochastic number of extraembryoni c cells escape imprinting. Second, contrary to conventional thinking, we wo uld like to consider the possibility that the paternal X might actually be transmitted to the zygote as a pre-inactivated chromosome. In this model, t he gamete initiates and establishes imprinted XCl, while the zygote maintai ns the pre-established pattern of gametic inactivation. Finally, we hypothe size that the inabsolute nature of imprinting is caused by imperfect zygoti c maintenance. We propose that the mouse represents a transitional stage in the evolution of random XCl from an absolutely imprinted mechanism.