DEVELOPMENTALLY-REGULATED XIST PROMOTER SWITCH MEDIATES INITIATION OFX-INACTIVATION

Developmental regulation of the mouse Xist gene at the onset of X chro mosome inactivation is mediated by RNA stabilization. Here, we show th at alternate promoter usage gives rise to distinct stable and unstable RNA isoforms. Unstable Xist transcript initiates at a novel upstream promoter, whereas stable Xist RNA is transcribed from the previously i dentified promoter and from a novel downstream promoter. Analysis of c ells undergoing X inactivation indicates that a developmentally regula ted promoter switch mediates stabilization and accumulation of Xist RN A on the inactive X chromosome.