STABILIZATION OF XIST RNA MEDIATES INITIATION OF X-CHROMOSOME INACTIVATION

The onset of X inactivation is preceded by a marked increase in the le vel of Xist RNA. Here we demonstrate that increased stability of Xist RNA is the primary determinant of developmental up-regulation. Unstabl e transcript is produced by both alleles in XX ES cells and in XX embr yos prior to the onset of random X inactivation. Following differentia tion, transcription of unstable RNA from the active X chromosome allel e continues for a period following stabilization and accumulation of t ranscript on the inactive X allele. We discuss the implications of the se findings in terms of models for the initiation of random and imprin ted X inactivation.