In XX female mammals, the inactivation of one X chromosome during development equalises the levels of X-linked gene products in females with levels in males. The Xist locus regulates X inactivation by producing Xist, a non-coding RNA that coats and silences the chromosome from which it is transcribed. Now, on p. , Neil Brockdorff and co-workers analyse X inactivation in XistINV mice, which carry a mutation in which a conserved region of Xist exon 1 is inverted. Inheritance of XistINV on the maternal X chromosome in female embryos results in secondary non-random X inactivation, they report, which indicates that the inversion affects Xist-mediated silencing but not Xist gene regulation. Moreover, XistINV inheritance on the paternal X chromosome leads to embryonic lethality because of failed imprinted X inactivation in extra-embryonic tissues. Other analyses show that XistINV RNA localises in cis to the X chromosome but with reduced efficiency. Thus, the researchers conclude, conserved Xist exon 1 sequences are important for Xist RNA localisation and, consequently, X-linked gene silencing.
