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H4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensabe for inducing gene silencing

2021-02-19Journal article Open access
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dc.contributor.authorTjalsma, Sjoerd J. D.
dc.contributor.authorHori, Mayako
dc.contributor.authorSato, Yuko
dc.contributor.authorBousard, Aurelie
dc.contributor.authorOhi, Akito
dc.contributor.authorRaposo, Ana Cláudia
dc.contributor.authorRoensch, Julia
dc.contributor.authorLe Saux, Agnes
dc.contributor.authorNogami, Jumpei
dc.contributor.authorMaehara, Kazumitsu
dc.contributor.authorKujirai, Tomoya
dc.contributor.authorHanda, Tetsuya
dc.contributor.authorBagés-Arnal, Sandra
dc.contributor.authorOhkawa, Yasuyuki
dc.contributor.authorKurumizaka, Hitoshi
dc.contributor.authorda Rocha, Simão T.
dc.contributor.authorŻylicz, Jan J.
dc.contributor.authorKimura, Hiroshi
dc.contributor.authorHeard, Edith
dc.date.accessioned2021-02-23T13:58:53Z
dc.date.available2021-02-23T13:58:53Z
dc.date.issued2021-02-19
dc.description© 2021 EMBO. This is an open access article under the terms of the Creative Commons Attribution License,which permits use, distribution and reproduction in any medium, provided the original work is properly cited.pt_PT
dc.description.abstractDuring X chromosome inactivation (XCI), in female placental mammals, gene silencing is initiated by the Xist long non-coding RNA. Xist accumulation at the X leads to enrichment of specific chromatin marks, including PRC2-dependent H3K27me3 and SETD8-dependent H4K20me1. However, the dynamics of this process in relation to Xist RNA accumulation remains unknown as is the involvement of H4K20me1 in initiating gene silencing. To follow XCI dynamics in living cells, we developed a genetically encoded, H3K27me3-specific intracellular antibody or H3K27me3-mintbody. By combining live-cell imaging of H3K27me3, H4K20me1, the X chromosome and Xist RNA, with ChIP-seq analysis we uncover concurrent accumulation of both marks during XCI, albeit with distinct genomic distributions. Furthermore, using a Xist B and C repeat mutant, which still shows gene silencing on the X but not H3K27me3 deposition, we also find a complete lack of H4K20me1 enrichment. This demonstrates that H4K20me1 is dispensable for the initiation of gene silencing, although it may have a role in the chromatin compaction that characterises facultative heterochromatin.pt_PT
dc.description.sponsorshipThis work was supported by Fundação para a Ciência e Tecnologia (S.T.d.R), project grants PTDC/BIA‐ MOL/29320/2017 IC&DT (A. C. R. & S.T.d.R), CEECUIND/01234/207 (S.T.d.R), and SFRH/BD/137099/2018 (A.C.R.), by an ERC Advanced Investigator award ERC‐ADG‐2014 671027 attributed to E.H., Sir Henry Wellcome Postdoctoral Fellowship (J.J.Z.), Japan Society for the Promotion of Science KAKENHI grants (JP17KK0143 and JP20K06484 to Y.S., JP19H04970, JP19H03158 and JP20H05393 to K.M., JP17K17719 to T.H., JP18H05534 to H.Ku, JP18H05527 and JP20H00456 to Y.O., JP17H01417 and JP18H05527 to H.Ki), and Japan Science and Technology Agency (JST) CREST JPMJCR16G1 to T.K., H.Ku, Y.O. and H.Ki, PREST JPMJPR2026 to K.M., and ERATO JPMJER1901 to H.Ku. J.J.Z. is supported by core funding of The Novo Nordisk Foundation Center for Stem Cell Biology (Novo Nordisk Foundation grant number NNF17CC0027852). Open Access funding enabled and organized by Projekt DEAL.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEMBO Rep. 2021 Feb 19:e51989pt_PT
dc.identifier.doi10.15252/embr.202051989pt_PT
dc.identifier.eissn1460-2075
dc.identifier.issn0261-4189
dc.identifier.urihttp://hdl.handle.net/10451/46492
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherEMBOpt_PT
dc.relationPTDC/BIA‐MOL/29320/2017pt_PT
dc.relationCEECUIND/01234/207pt_PT
dc.relationFunctional dissection of the XIST non-coding RNA in X-chromosome inactivation in human ESCs
dc.relation.publisherversionhttps://www.embopress.org/journal/14693178pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectH4K20me1pt_PT
dc.subjectX inactivationpt_PT
dc.subjectEmbryonic stem cellspt_PT
dc.subjectHeterochromatinpt_PT
dc.subjectPolycombpt_PT
dc.titleH4K20me1 and H3K27me3 are concurrently loaded onto the inactive X chromosome but dispensabe for inducing gene silencingpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleFunctional dissection of the XIST non-coding RNA in X-chromosome inactivation in human ESCs
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F137099%2F2018/PT
oaire.citation.startPagee51989pt_PT
oaire.citation.titleEMBO reportspt_PT
person.familyNameBernardino Raposo
person.familyNameTeixeira da Rocha
person.givenNameAna Cláudia
person.givenNameSimão José
person.identifier.ciencia-id5319-3EE3-36F3
person.identifier.ciencia-id1310-8F0F-1387
person.identifier.orcid0000-0002-9683-7942
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication9331a22e-c445-4ef8-9f6e-f7df8a171dc9
relation.isAuthorOfPublication52b38b81-1fbe-42e0-9c6b-a334400ae3d6
relation.isAuthorOfPublication.latestForDiscovery9331a22e-c445-4ef8-9f6e-f7df8a171dc9
relation.isProjectOfPublication10872059-cf29-4ccd-82b2-acb6fb119cee
relation.isProjectOfPublication.latestForDiscovery10872059-cf29-4ccd-82b2-acb6fb119cee

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