E2F6 initiates stable epigenetic silencing of germline genes during embryonic development

Dahlet, Thomas; Truss, Matthias; Frede, Ute; Al Adhami, Hala; Bardet, Anaïs F.; Dumas, Michael; Vallet, Judith; Chicher, Johana; Hammann, Philippe; Kottnik, Sarah; Hansen, Peter; Luz, Uschi; Alvarez, Gonzalo; Auclair, Ghislain; Hecht, Jochen; Robinson, Peter N.; Hagemeier, Christian; Weber, Michael

E2F6 initiates stable epigenetic silencing of germline genes during embryonic development

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dc.contributor.author Dahlet, Thomas
dc.contributor.author Truss, Matthias
dc.contributor.author Frede, Ute
dc.contributor.author Al Adhami, Hala
dc.contributor.author Bardet, Anaïs F.
dc.contributor.author Dumas, Michael
dc.contributor.author Vallet, Judith
dc.contributor.author Chicher, Johana
dc.contributor.author Hammann, Philippe
dc.contributor.author Kottnik, Sarah
dc.contributor.author Hansen, Peter
dc.contributor.author Luz, Uschi
dc.contributor.author Alvarez, Gonzalo
dc.contributor.author Auclair, Ghislain
dc.contributor.author Hecht, Jochen
dc.contributor.author Robinson, Peter N.
dc.contributor.author Hagemeier, Christian
dc.contributor.author Weber, Michael
dc.date.accessioned 2022-05-20T05:52:13Z
dc.date.available 2022-05-20T05:52:13Z
dc.date.issued 2021
dc.description.abstract In mouse development, long-term silencing by CpG island DNA methylation is specifically targeted to germline genes; however, the molecular mechanisms of this specificity remain unclear. Here, we demonstrate that the transcription factor E2F6, a member of the polycomb repressive complex 1.6 (PRC1.6), is critical to target and initiate epigenetic silencing at germline genes in early embryogenesis. Genome-wide, E2F6 binds preferentially to CpG islands in embryonic cells. E2F6 cooperates with MGA to silence a subgroup of germline genes in mouse embryonic stem cells and in embryos, a function that critically depends on the E2F6 marked box domain. Inactivation of E2f6 leads to a failure to deposit CpG island DNA methylation at these genes during implantation. Furthermore, E2F6 is required to initiate epigenetic silencing in early embryonic cells but becomes dispensable for the maintenance in differentiated cells. Our findings elucidate the mechanisms of epigenetic targeting of germline genes and provide a paradigm for how transient repression signals by DNA-binding factors in early embryonic cells are translated into long-term epigenetic silencing during mouse development.
dc.description.sponsorship This work was supported by the European Research Council (ERC Consolidator grant number 615371 to M.W.), the Deutsche Forschungsgemeinschaft (DFG, grant number 63465200 to C.H.), and the ITI InnoVec of the University of Strasbourg, CNRS and Inserm (IdEx ANR-10-IDEX-0002, SFRI ANR-20-SFRI-0012). T.D. was recipient of a Doctoral fellowship from the French Ministry for Higher Education and Research. Mass spectrometry instrumentation was granted by the University of Strasbourg (IdEx Equipement mi-lourd 2015)
dc.format.mimetype application/pdf
dc.identifier.citation Dahlet T, Truss M, Frede U, Al Adhami H, Bardet AF, Dumas M et al. E2F6 initiates stable epigenetic silencing of germline genes during embryonic development. Nat Commun. 2021 Jun 11;12(1):3582. DOI:10.1038/s41467-021-23596-w
dc.identifier.doi http://dx.doi.org/10.1038/s41467-021-23596-w
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/53178
dc.language.iso eng
dc.publisher Nature Research
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/615371
dc.rights © Thomas Dahlet et al. 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Epigenètica
dc.subject.other Embriologia
dc.subject.other ADN -- Metilació
dc.subject.other Cèl·lules mare embrionàries
dc.title E2F6 initiates stable epigenetic silencing of germline genes during embryonic development
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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