Document Type
Article
Publication Date
6-11-2021
Publication Title
Nat Commun
Keywords
JGM
JAX Source
Nat Commun 2021 Jun 11; 12(1):3582
Volume
12
Issue
1
First Page
3582
Last Page
3582
ISSN
2041-1723
PMID
34117224
DOI
https://doi.org/10.1038/s41467-021-23596-w
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.
Recommended Citation
Dahlet T,
Truss M,
Frede U,
Al Adhami H,
Bardet A,
Dumas M,
Vallet J,
Chicher J,
Hammann P,
Kottnik S,
Hansen P,
Luz U,
Alvarez G,
Auclair G,
Hecht J,
Robinson P,
Hagemeier C,
Weber M.
E2F6 initiates stable epigenetic silencing of germline genes during embryonic development. Nat Commun 2021 Jun 11; 12(1):3582
Comments
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