title: Mammalian X chromosome inactivation.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jaenisch
authors.forename: C
authors.initials: C
authors.lastname: Beard
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Marahrens
authors.forename: B
authors.initials: B
authors.lastname: Panning
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008322:Mammals / Q000235:genetics; D012313:RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA; D012313:RNA