Perturbed maintenance of transcriptional repression on the inactive X-chromosome in the mouse brain after Xist deletion

Epigenetics & Chromatin
Robin L AdrianseAntonio Bedalov

Abstract

The long noncoding RNA Xist is critical for initiation and establishment of X-chromosome inactivation during embryogenesis in mammals, but it is unclear whether its continued expression is required for maintaining X-inactivation in vivo. By using an inactive X-chromosome-linked MeCP2-GFP reporter, which allowed us to enumerate reactivation events in the mouse brain even when they occur in very few cells, we found that deletion of Xist in the brain after establishment of X-chromosome inactivation leads to reactivation in 2-5% of neurons and in a smaller fraction of astrocytes. In contrast to global loss of both H3 lysine 27 trimethylation (H3K27m3) and histone H2A lysine 119 monoubiquitylation (H2AK119ub1) we observed upon Xist deletion, alterations in CpG methylation were subtle, and this was mirrored by only minor alterations in X-chromosome-wide gene expression levels, with highly expressed genes more prone to both derepression and demethylation compared to genes with low expression level. Our results demonstrate that Xist plays a role in the maintenance of histone repressive marks, DNA methylation and transcriptional repression on the inactive X-chromosome, but that partial loss of X-dosage compensation in the absence of Xis...Continue Reading

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Citations

Jul 24, 2020·BMC Genomics·Patricia C Lopes, Barbara König
Feb 12, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lin YangJeannie T Lee
Jan 28, 2021·International Journal of Molecular Sciences·Ali YounessJean-Charles Guéry
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Wenlun WangLingyun Zhu
Oct 12, 2021·Frontiers in Cell and Developmental Biology·Vasco M BarretoAnne-Valerie Gendrel
Nov 28, 2021·Nature Reviews. Genetics·Daniel Andergassen, John L Rinn

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Methods Mentioned

BETA
pull-down
PCR
RNA-seq
transgenic

Software Mentioned

Real Time Analysis
bcl2fastq Conversion
Illumina

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