MONFORT, Asun, Giulio DI MININ, Andreas POSTLMAYR, R. FREIMANN, Fabiana ARIETI, Stéphane THORE and Anton WUTZ. Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells. Cell Reports. CAMBRIDGE: Cell Press, 2015, vol. 12, No 4, p. 554-561. ISSN 2211-1247. doi:10.1016/j.celrep.2015.06.067.
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Basic information
Original name Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells
Authors MONFORT, Asun (756 Switzerland), Giulio DI MININ (756 Switzerland), Andreas POSTLMAYR (756 Switzerland), R. FREIMANN (756 Switzerland), Fabiana ARIETI (380 Italy, guarantor, belonging to the institution), Stéphane THORE (250 France) and Anton WUTZ (756 Switzerland).
Edition Cell Reports, CAMBRIDGE, Cell Press, 2015, 2211-1247.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 7.870
RIV identification code RIV/00216224:14740/15:00085377
Organization unit Central European Institute of Technology
Doi http://dx.doi.org/10.1016/j.celrep.2015.06.067
UT WoS 000358742300003
Keywords in English INACTIVE X-CHROMOSOME; DOSAGE COMPENSATION; SAF-A; RNA; SHARP; MICE; LOCALIZATION; MAINTENANCE; ACTIVATION; SUPPRESSOR
Tags OA, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Eva Špillingová, učo 110713. Changed: 5. 4. 2016 10:11.
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.
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