XISTing Synergy

Science Signaling  23 Sep 2008:
Vol. 1, Issue 38, pp. ec333
DOI: 10.1126/scisignal.138ec333

In female mammalian embryos, one of the two X chromosomes must be shut down so that X-linked gene expression mirrors the equivalent XY male embryo. Expression of the X-linked Xist gene ensures repression of the X chromosome of which it is part. At the very earliest stages of embryogenesis, initially paternally imprinted X inactivation is lost in the inner cell mass (which will form the embryo proper), along with the associated Xist expression, and the paternal X chromosome is reactivated, before random X inactivation is established as the inner cell mass differentiates. Using embryonic stem cells, Navarro et al. show that the genes critical for maintaining the pluripotency of the inner cell mass at this very early stage of development--Nanog, Oct3/4, and Sox2--also act synergistically to transiently repress Xist until cellular differentiation is initiated, thereby directly coupling the control of Xist expression to pluripotency.

P. Navarro, I. Chambers, V. Karwacki-Neisius, C. Chureau, C. Morey, C. Rougeulle, P. Avner, Molecular coupling of Xist regulation and pluripotency. Science 321, 1693-1695 (2008). [Abstract] [Full Text]