E2F6 initiates stable epigenetic silencing of germline genes during embryonic development

Autor: 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
Přispěvatelé: 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)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: 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)
ISSN: 2041-1723
DOI: 10.1038/s41467-021-23596-w⟩
Popis: 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.
Databáze: OpenAIRE
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