title: Evidence that random and imprinted Xist expression is controlled by preemptive methylation.
abstract: The mouse Xist gene is expressed exclusively from the inactive X chromosome and may control the initiation of X inactivation. We show that in somatic tissues the 5' end of the silent Xist allele on the active X chromosome is fully methylated, while the expressed allele on the inactive X is completely unmethylated. In tissues that undergo imprinted paternal Xist expression and imprinted X inactivation, the paternal Xist allele is unmethylated, and the silent maternal allele is fully methylated. In the male germline, a developmentally regulated demethylation of Xist occurs at the onset of meiosis and is retained in mature spermatozoa. This may be the cause of imprinted expression of the paternal Xist allele. A role for methylation in the control of Xist expression is further supported by the finding that in differentiating embryonic stem cells during the initiation of X inactivation, differential methylation of Xist alleles precedes the onset of Xist expression.
authors.affiliation: Section of Comparative Biology, Medical Research Council Clinical Research Centre, Harrow, England.
authors.forename: D P
authors.initials: DP
authors.lastname: Norris
authors.forename: D
authors.initials: D
authors.lastname: Patel
authors.forename: G F
authors.initials: GF
authors.lastname: Kay
authors.forename: G D
authors.initials: GD
authors.lastname: Penny
authors.forename: N
authors.initials: N
authors.lastname: Brockdorff
authors.forename: S A
authors.initials: SA
authors.lastname: Sheardown
authors.forename: S
authors.initials: S
authors.lastname: Rastan
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004303:Dosage Compensation, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007173:Imprinting, Psychological; D008297:Male; D008540:Meiosis; D008745:Methylation; D051379:Mice; D008815:Mice, Inbred Strains; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D013094:Spermatozoa / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014960:X Chromosome / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA