Dahlet Thomas, Truss Matthias, Frede Ute, Adhami Hala Al, Bardet Anaïs F., Dumas Michael, Vallet Judith, Chicher Johana, Hammann Philippe, Kottnik Sarah, Hansen Peter, Luz Uschi, Alvarez Gonzalo, Auclair Ghislain, Hecht Jochen, Robinson Peter N., Hagemeier Christian, Weber Michael
E2F6 initiates stable epigenetic silencing of germline genes during embryonic development Journal Article
In: Nature Communications, vol. 12, no. 1, pp. 3582, 2021, ISSN: 2041-1723.
Abstract | Links | BibTeX | Tags: Animals, Binding Sites, Cell Differentiation, CpG Islands, CRISPR-Cas Systems, DNA Methylation, E2F6 Transcription Factor, Embryonic Development, Epigenesis, Gene Silencing, Genetic, Germ Cells, Knockout, Mice, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 1, PPSE, RNA, Small Interfering
@article{dahlet_e2f6_2021,
title = {E2F6 initiates stable epigenetic silencing of germline genes during embryonic development},
author = {Thomas Dahlet and Matthias Truss and Ute Frede and Hala Al Adhami and Anaïs F. Bardet and Michael Dumas and Judith Vallet and Johana Chicher and Philippe Hammann and Sarah Kottnik and Peter Hansen and Uschi Luz and Gonzalo Alvarez and Ghislain Auclair and Jochen Hecht and Peter N. Robinson and Christian Hagemeier and Michael Weber},
doi = {10.1038/s41467-021-23596-w},
issn = {2041-1723},
year = {2021},
date = {2021-06-01},
journal = {Nature Communications},
volume = {12},
number = {1},
pages = {3582},
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.},
keywords = {Animals, Binding Sites, Cell Differentiation, CpG Islands, CRISPR-Cas Systems, DNA Methylation, E2F6 Transcription Factor, Embryonic Development, Epigenesis, Gene Silencing, Genetic, Germ Cells, Knockout, Mice, Mouse Embryonic Stem Cells, Polycomb Repressive Complex 1, PPSE, RNA, Small Interfering},
pubstate = {published},
tppubtype = {article}
}