In mammals, X-inactivation compensates for the difference in X-linked gene dosage between the sexes. Key to this process is the non-coding transcript Xist, which is expressed by the inactive X and coats it. Its antisense non-coding gene, Tsix, which is spliced like a protein-coding RNA, also plays a crucial role in X-inactivation, possibly by forming a sense-antisense RNA pair with Xist, which it regulates. Sado and co-workers now provide new insights into how Tsix regulates Xist expression by showing that Tsix splicing is not required to establish Xist silencing (see p. 4925). By genetically eliminating the splice products of Tsix in mouse embryos,the researchers surprisingly discovered that the Xist locus is stably repressed in the absence of Tsix splicing and that repressive chromatin forms as normal at the Xist promoter. They conclude,therefore, that Tsix splice products are not needed to silence Xist. Whether unspliced Tsix RNA is required for Tsix-mediated Xist silencing, or whether Tsixtranscription per se is sufficient, remains to be discovered.