Tsix, a gene antisense to Xist at the X-inactivation centre

In mammals, dosage compensation is achieved by X inactivation(1) and is reg ulated in cis by the X-inactivation centre(2) (Xic) and Xist (refs 3-5). Th e Xic controls X-chromosome counting, choice of X to inactivate and initiat ion of silencing. Xic action culminates in a change in Xist RNA property fr om a scarce, unstable RNA (refs 6,7) to highly expressed Xist RNA that coat s the future inactive X (ref. 8). Deleting a 65-kb region downstream of Xis t results in constitutive Xist expression and X inactivation, implying the presence of a cis-regulatory element(9). In this region, we now report the discovery of a gene antisense to Xist. Tsix is a 40-kb RNA originating 15 k b downstream of Xist and transcribed across the Xist locus. Tsix sequence i s conserved at the human XIC. Tsix RNA has no conserved ORFs, is seen exclu sively in the nucleus and is localized at Xic. Before the onset of X inacti vation, Tsix is expressed from both X chromosomes. At the onset of X inacti vation, Tsix expression becomes monoallelic, is associated with the future active X and persists until Xist is turned off. Tsix is not found on the in active X once cells enter the X-inactivation pathway. Tsix has features sug gesting a role in regulating the early steps of X inactivation, but not the silencing step.