Evidence that random and imprinted Xist expression is controlled by preemptive methylation.
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.
Norris
D P
DP
Section of Comparative Biology, Medical Research Council Clinical Research Centre, Harrow, England.
Patel
D
D
Kay
G F
GF
Penny
G D
GD
Brockdorff
N
N
Sheardown
S A
SA
Rastan
S
S
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*
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D014157:Transcription Factors; C077885:XIST non-coding RNA