XIST EXPRESSION IS REPRESSED WHEN X INACTIVATION IS REVERSED IN HUMANPLACENTAL CELLS - A MODEL FOR STUDY OF XIST REGULATION

Considerable evidence suggests that the X inactive transcript gene, XI ST/Xist, has a role in the initial steps of X chromosome inactivation in the female mammalian embryo. It is transcribed exclusively from ina ctive X chromosomes, and its noncoding transcript seems to be essentia l for cis inactivation. Unexpected for a developmental gene, XIST cont inues to be expressed in adult somatic cells. To determine the effect of reversal of inactivation on the expression of XIST, we studied huma n X chromosomes that had been induced to reverse X inactivation by hyb ridization of chronic villi cells from term placentas with mouse A9 ce lls. In nine hybrids with a reactivated X chromosome, XIST was either not expressed or expressed much less than the locus on the inactive X chromosome in the chorionic villi cells from which they were derived. The repressibility of XIST by reversal of inactivation in these placen tal cells mirrors events that occur during the ontogeny of oocytes and indicates that the locus is subject to regulation in somatic cells lo ng after inactivation is established in the embryo. The small residual XIST activity from these active chromosomes suggests that low levels of XIST expression do not interfere with chromosome activity and raise s the possibility that the induction of cis inactivation requires a ce rtain level of XIST transcription. The chorionic villi hybrids provide an experimental system to study the developmental regulation of XIST.