We are now scrutinizing the destiny of cells with different patterns of Xci. Next, we plan to follow up in ex vivo « implanting » embryos, and to build a system which will allow us to see gene silencing when it occurs.
Initiation of X chromosome inactivation : is it a « Swiss Clock » or « Just A Mess » ?
Philippe Clerc et al.
The necessity to see.
Xci ensures dosage compensation of X-linked genes between male (XY) and female (XX) mammal embryos. The final outcome of Xci is that all female somatic cells carry a single transcriptionally active X chromosome just like male cells do. How precisely this is achieved is still a matter of debate. Some data from the litterature suggest that sophisticated early mechanisms of chromosome pairing are involved. Other data suggest that late selection operates after stochastic events. A swiss clock or just a mess, which is right ? Maybe both.
We believe that analysing the process in live cells is the only way to find out. However, in the female mouse embryo, Xci is initiated just after implantation within the uterus wall (day 5.5-6.0 after fertilisation). This innermost localisation and the necessity for tagging the molecular players explain why nobody has yet seen Xci at the time when it occurs in the live embryo.
Let’s see now.
At the initiation of random X chromosome inactivation (Xci), a non-coding RNA (Xist) followed by Polycomb Group proteins accumulate on the territory occupied by the future inactive X chromosome within the nucleus.
We fluorescently tagged a polycomb protein in XX murine embryonic stem cells (ES). Since ES cells initiate Xci when induced to leave pluripotency, we could see for the first time the inactive X chromosomes in the nuclei of live cells:
From there.
We are now scrutinizing the destiny of cells with different patterns of Xci. Next, we plan to follow up in ex vivo « implanting » embryos, and to build a system which will allow us to see gene silencing when it occurs.