E2F6 initiates stable epigenetic silencing of germline genes during embryonic development.

Autor: Dahlet T; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Truss M; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. matthias.truss@charite.de., Frede U; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany., Al Adhami H; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Bardet AF; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Dumas M; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Vallet J; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Chicher J; Plateforme protéomique Strasbourg Esplanade, CNRS, University of Strasbourg, Strasbourg, France., Hammann P; Plateforme protéomique Strasbourg Esplanade, CNRS, University of Strasbourg, Strasbourg, France., Kottnik S; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany., Hansen P; Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany., Luz U; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany., Alvarez G; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany., Auclair G; University of Strasbourg, Strasbourg, France.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France., Hecht J; Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.; Centre for Genomic Regulation, Barcelona, Spain., Robinson PN; Berlin Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.; Jackson Laboratory for Genomic Medicine, Farmington, CT, USA., Hagemeier C; Pediatric Oncology, Labor für Pädiatrische Molekularbiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. christian.hagemeier@charite.de., Weber M; University of Strasbourg, Strasbourg, France. michael.weber@unistra.fr.; CNRS UMR7242, Biotechnology and Cell Signaling, Illkirch, France. michael.weber@unistra.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jun 11; Vol. 12 (1), pp. 3582. Date of Electronic Publication: 2021 Jun 11.
DOI: 10.1038/s41467-021-23596-w
Abstrakt: 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.
Databáze: MEDLINE
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