The non-coding RNA Xist plays a key role in the process of X chromosome inactivation (XCI) and is thus essential for dosage compensation of X-linked genes in females. The 5′ region of Xist RNA contains a conserved element termed the A-repeat that is required for the silencing function of Xist in embryonic stem cells, but how this region functions during development is unclear. Now, Takashi Sado and co-workers explore this by introducing into mice a mutated Xist allele that produces Xist RNA lacking the A-repeat region (p. 2784). They first report that imprinted XCI is compromised upon paternal transmission of this allele. The authors further show that the mutant form of Xist is able to coat the X chromosome but fails to silence it in embryonic and extraembryonic tissues. Surprisingly, however, mutant Xist RNA is still able to silence a subset of genes in the trophoblast. Finally, the authors reveal that the failure of imprinted XCI has a more significant impact on genome-wide gene expression than expected; changes in the expression of both X-linked and autosomal genes are observed. Together these findings provide new insights into Xist-mediated gene silencing but also raise the intriguing possibility that dosage compensation regulates X-linked genes as well as gene expression more globally.