Loss of methylation activates Xist in somatic but not in embryonic cells

The mouse Xist gene, which is expressed only from the inactive X chromosome, is thought to play a role in the initiation of X inactivation. The 5' end of this gene is fully methylated on the active X chromosome and completely demethylated on the inactive X chromosome, suggesting that DNA methyl...

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Bibliographic Details
Published in:Genes & development 1995-10, Vol.9 (19), p.2325-2334
Main Authors: Beard, C, Li, E, Jaenisch, R
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Blotting, Southern
Cell Differentiation
Cell Line
DNA Modification Methylases - deficiency
DNA Modification Methylases - genetics
DNA Modification Methylases - metabolism
DNA Primers
Embryo, Mammalian - metabolism
Female
Gene Expression Regulation, Developmental - genetics
Genotype
Homozygote
Male
Methylation
Mice
Molecular Sequence Data
Mutation - genetics
Ribonucleases - metabolism
RNA, Long Noncoding
RNA, Untranslated
Stem Cells - metabolism
Transcription Factors - genetics
Transcription, Genetic - genetics
X Chromosome - genetics
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Summary:The mouse Xist gene, which is expressed only from the inactive X chromosome, is thought to play a role in the initiation of X inactivation. The 5' end of this gene is fully methylated on the active X chromosome and completely demethylated on the inactive X chromosome, suggesting that DNA methylation may be involved in controlling allele-specific transcription of this gene. To directly investigate the importance of DNA methylation in the control of Xist expression, we have examined its methylation patterns and expression in ES cells and embryos that are deficient in DNA methyltransferase activity. We report here that demethylation of the Xist locus in male mutant embryos induces Xist expression, thus establishing a direct link between demethylation and expression of the Xist gene in the postgastrulation embryo. The transcriptional activity of Xist in undifferentiated ES cells, however, appears to be independent of its methylation status. These results suggest that methylation may only become essential for Xist repression after ES cells have differentiated or after the embryo has undergone gastrulation.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.9.19.2325