E2F6 initiates stable epigenetic silencing of germline genes during embryonic development
| العنوان: | E2F6 initiates stable epigenetic silencing of germline genes during embryonic development |
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| المؤلفون: | Philippe Hammann, Hala Al Adhami, Gonzalo Alvarez, Matthias Truss, Sarah Kottnik, Christian Hagemeier, Johana Chicher, Judith Vallet, Anaïs F. Bardet, Jochen Hecht, Ute Frede, Thomas Dahlet, Michael Weber, Michael Dumas, Uschi Luz, Ghislain Auclair, Peter Hansen, Peter N. Robinson |
| المساهمون: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), ANR-20-SFRI-0012,STRAT'US,Façonner les talents en formation et en recherche à l'Université de Strasbourg(2020), European Project: 615371,EC:FP7:ERC,ERC-2013-CoG,TRANSMETH(2014), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS) |
| المصدر: | Nature Communications Nature Communications, 2021, 12, pp.3582. ⟨10.1038/s41467-021-23596-w⟩ Nature Communications, Nature Publishing Group, 2021, 12, pp.3582. ⟨10.1038/s41467-021-23596-w⟩ Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Epigenomics, Cellular differentiation, General Physics and Astronomy, E2F6 Transcription Factor, Germline, Epigenesis, Genetic, Mice, 0302 clinical medicine, genetics, RNA, Small Interfering, Mice, Knockout, Polycomb Repressive Complex 1, Multidisciplinary, DNA methylation, Cèl·lules mare embrionàries, Gene silencing, Cell Differentiation, Mouse Embryonic Stem Cells, ADN -- Metilació, Cell biology, CpG site, Epigenetic memory, Science, Embryonic Development, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Epigenetics, Transcription factor, Binding Sites, Embriologia, Sciences du Vivant [q-bio]/Biologie du développement, General Chemistry, metabolism, Epigenètica, Embryonic stem cell, 030104 developmental biology, Germ Cells, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, CpG Islands, CRISPR-Cas Systems, 030217 neurology & neurosurgery |
| الوصف: | 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. DNA methylation targets CpG island promoters of germline genes to repress their expression in mouse somatic cells. Here the authors show that a transcription factor E2F6 is required to target CpG island DNA methylation and epigenetic silencing to germline genes during early mouse development. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f7ab6abc4ce0075028f98d18c18beb4e https://hal.science/hal-03380281/file/Dahlet_NatComm_2021.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f7ab6abc4ce0075028f98d18c18beb4e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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