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Novartis Found Symp. 1998;214:200-9; discussion 209-13, 228-32.

Mammalian X chromosome inactivation.

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  • 1Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.


X chromosome inactivation in mammals requires expression of the gene Xist, which maps to the X chromosome inactivation centre (Xic) and encodes an untranslated RNA. Truncation of Xist RNA by gene targeting is lethal for female embryos and prevents the inactivation of the X chromosome carrying the deletion. This indicates that Xist RNA is necessary for initiation and propagation of the inactivation process. Xist is transcribed from the inactive X and its expression is silenced by DNA methylation, suggesting that methylation is crucial for shielding the active X chromosome against the inactivation process. Gene transfer experiments using transgenes the size of yeast artificial chromosomes have determined that a 450 kb fragment of DNA carrying Xist acts as an inactivation centre and is sufficient for initiation, propagation and maintenance of the inactive state. The elements for counting and choosing X chromosomes are part of the transgene. We have shown that X inactivation is mediated by a post-translational mechanism, i.e. the stabilization of Xist RNA, rather than by the regulation of the Xist promoter.

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