E2F6 initiates stable epigenetic silencing of germline genes during embryonic development

Thomas Dahlet, Matthias Truss (), Ute Frede, Hala Al Adhami, Anaïs F. Bardet, Michael Dumas, Judith Vallet, Johana Chicher, Philippe Hammann, Sarah Kottnik, Peter Hansen, Uschi Luz, Gonzalo Alvarez, Ghislain Auclair, Jochen Hecht, Peter N. Robinson, Christian Hagemeier () and Michael Weber ()
Additional contact information
Thomas Dahlet: University of Strasbourg
Matthias Truss: Charité - Universitätsmedizin Berlin
Ute Frede: Charité - Universitätsmedizin Berlin
Hala Al Adhami: University of Strasbourg
Anaïs F. Bardet: University of Strasbourg
Michael Dumas: University of Strasbourg
Judith Vallet: University of Strasbourg
Johana Chicher: University of Strasbourg
Philippe Hammann: University of Strasbourg
Sarah Kottnik: Charité - Universitätsmedizin Berlin
Peter Hansen: Charité Universitätsmedizin Berlin
Uschi Luz: Charité - Universitätsmedizin Berlin
Gonzalo Alvarez: Charité - Universitätsmedizin Berlin
Ghislain Auclair: University of Strasbourg
Jochen Hecht: Charité Universitätsmedizin Berlin
Peter N. Robinson: Charité Universitätsmedizin Berlin
Christian Hagemeier: Charité - Universitätsmedizin Berlin
Michael Weber: University of Strasbourg

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23596-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23596-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23596-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().