Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells

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Author
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Date
2015-07Type
- Journal Article
Citations
Cited 156 times in
Web of Science
Cited 159 times in
Scopus
ETH Bibliography
yes
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Abstract
In mammals, the noncoding Xist RNA triggers transcriptional silencing of one of the two X chromosomes in female cells. Here, we report a genetic screen for silencing factors in X chromosome inactivation using haploid mouse embryonic stem cells (ESCs) that carry an engineered selectable reporter system. This system was able to identify several candidate factors that are genetically required for chromosomal repression by Xist. Among the list of candidates, we identify the RNA-binding protein Spen, the homolog of split ends. Independent validation through gene deletion in ESCs confirms that Spen is required for gene repression by Xist. However, Spen is not required for Xist RNA localization and the recruitment of chromatin modifications, including Polycomb protein Ezh2. The identification of Spen opens avenues for further investigation into the gene-silencing pathway of Xist and shows the usefulness of haploid ESCs for genetic screening of epigenetic pathways. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000102870Publication status
publishedExternal links
Journal / series
Cell ReportsVolume
Pages / Article No.
Publisher
ElsevierOrganisational unit
03978 - Wutz, Anton / Wutz, Anton
Funding
152814 - X chromosome reactivation in development and transformation (SNF)
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Show all metadata
Citations
Cited 156 times in
Web of Science
Cited 159 times in
Scopus
ETH Bibliography
yes
Altmetrics