Show simple item record

dc.contributor.authorBorensztein, Mauden
dc.contributor.authorSyx, Len
dc.contributor.authorAncelin, Ken
dc.contributor.authorDiabangouaya, Pen
dc.contributor.authorPicard, Cen
dc.contributor.authorLiu, Ten
dc.contributor.authorLiang, J-Ben
dc.contributor.authorVassilev, Ien
dc.contributor.authorGalupa, Ren
dc.contributor.authorServant, Nen
dc.contributor.authorBarillot, Een
dc.contributor.authorSurani, Azimen
dc.contributor.authorChen, C-Jen
dc.contributor.authorHeard, Een
dc.date.accessioned2017-03-13T10:36:00Z
dc.date.available2017-03-13T10:36:00Z
dc.date.issued2017-03-01en
dc.identifier.issn1545-9993
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/263041
dc.description.abstractThe long noncoding RNA Xist is expressed from only the paternal X chromosome in mouse preimplantation female embryos and mediates transcriptional silencing of that chromosome. In females, absence of Xist leads to postimplantation lethality. Here, through single-cell RNA sequencing of early preimplantation mouse embryos, we found that the initiation of imprinted X-chromosome inactivation absolutely requires Xist. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst and to failure to activate the extraembryonic pathway that is essential for postimplantation development. We also demonstrate that the expression dynamics of X-linked genes depends on the strain and parent of origin as well as on the location along the X chromosome, particularly at the first 'entry' sites of Xist. This study demonstrates that dosage-compensation failure has an effect as early as the blastocyst stage and reveals genetic and epigenetic contributions to orchestrating transcriptional silencing of the X chromosome during early embryogenesis.
dc.description.sponsorshipThis work was funded by a fellowship of Région Ile-de-France (DIM STEMP OLE) to M.B., the Paris Alliance of Cancer Research Institutes (PACRI-ANR) to LS and ERC Advanced Investigator award (ERC-2010-AdG–No.250367), EU FP7 grants SYBOSS (EU 7th Framework G.A. no. 242129) and MODHEP (EU 7th Framework G.A. no. 259743), La Ligue, Fondation de France, Labex DEEP (ANR-11-LBX-0044) part of the IDEX Idex PSL (ANR-10-IDEX-0001-02 PSL) and ABS4NGS (ANR-11-BINF-0001) to E.H and France Genomique National infrastructure (ANR-10-INBS09) to EH, NS, EB.
dc.languageengen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.titleXist-dependent imprinted X inactivation and the early developmental consequences of its failureen
dc.typeArticle
prism.endingPage233
prism.issueIdentifier3en
prism.publicationDate2017en
prism.publicationNameNature Structural and Molecular Biologyen
prism.startingPage226
prism.volume24en
dc.identifier.doi10.17863/CAM.8337
dcterms.dateAccepted2017-01-20en
rioxxterms.versionofrecord10.1038/nsmb.3365en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-03-01en
dc.contributor.orcidBorensztein, Maud [0000-0002-4378-5018]
dc.contributor.orcidSurani, Azim [0000-0002-8640-4318]
dc.identifier.eissn1545-9985
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEC FP7 CP (242129)
cam.issuedOnline2017-01-30en
rioxxterms.freetoread.startdate2017-07-30


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record