X-CHROMOSOME INACTIVATION IS MEDIATED BY XIST RNA STABILIZATION

Low level Xist expression can be detected from both active X chromosom es (Xa) in female embryonic stem cells prior to X inactivation. After differentiation, Xist is expressed at high levels only from the inacti ve X chromosome (Xi). Differentiating female cells increase Xist expre ssion from the Xi prior to silencing low level Xist expression from th e Xa. The transition from low level to high level expression is regula ted by the stabilization of Xist transcripts at the Xi. We suggest tha t these developmentally modulated changes in Xist expression are regul ated by several different mechanisms: factors that stabilize Xist tran scripts at the Xi, an activity that blocks this stabilization at the X a, and a mechanism that silences low level Xist expression from the Xa .