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.

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This article is licensed under a Creative Commons Attribution 4.0 International License.

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