Xist and its antisense partner, Tsix, encode non-coding RNAs and play key roles in X chromosome inactivation. Targeted disruption of Tsix causes ectopic expression of Xist in the extraembryonic tissues upon maternal transmission, which subsequently results in embryonic lethality due to inactivation of both X chromosomes in females and a single X chromosome in males. Tsix, therefore, plays a crucial role in maintaining the silenced state of Xist in cis and regulates the imprinted X inactivation in the extraembryonic tissues. In this study, we examined the effect of Tsix disruption on Xist expression in the embryonic lineage using embryonic stem (ES) cells as a model system. Upon differentiation, Xist is ectopically activated in a subset of the nuclei of male ES cells harboring the Tsix-deficient X chromosome. Such ectopic expression, however, eventually ceased during prolonged culture. It is likely that surveillance by the X chromosome counting mechanism somehow shuts off the ectopic expression of Xist before inactivation of the X chromosome.
All Science Journal Classification (ASJC) codes
- Molecular Biology