Publications
2021
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}
}
1994
Meister Marie, Braun A, Kappler Christine, Reichhart Jean-Marc, Hoffmann Jules A
Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter Journal Article
In: EMBO J., vol. 13, no. 24, pp. 5958–5966, 1994, ISSN: 0261-4189.
Abstract | BibTeX | Tags: Animals, Anti-Infective Agents, Base Sequence, beta-Galactosidase, DNA Mutational Analysis, Female, Gene Expression Regulation, Genetic, Genetically Modified, Germ Cells, hoffmann, Insect Hormones, Insect Proteins, M3i, Male, Models, Nucleic Acid, Promoter Regions, Recombinant Fusion Proteins, reichhart, Repetitive Sequences, Transformation
@article{meister_insect_1994,
title = {Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter},
author = {Marie Meister and A Braun and Christine Kappler and Jean-Marc Reichhart and Jules A Hoffmann},
issn = {0261-4189},
year = {1994},
date = {1994-12-01},
journal = {EMBO J.},
volume = {13},
number = {24},
pages = {5958--5966},
abstract = {Diptericins are antibacterial polypeptides which are strongly induced in the fat body and blood cells of dipteran insects in response to septic injury. The promoter of the single-copy, intronless diptericin gene of Drosophila contains several nucleotide sequences homologous to mammalian cis-regulatory motifs involved in the control of acute phase response genes. Extending our previous studies on the expression of the diptericin gene, we now report a quantitative analysis of the contribution of various putative regulatory elements to the bacterial inducibility of this gene, based on the generation of 60 transgenic fly lines carrying different elements fused to a reporter gene. Our data definitively identify two Kappa B-related motifs in the proximal promoter as the sites conferring inducibility and tissue-specific expression to the diptericin gene. These motifs alone, however, mediate only minimal levels of expression. Additional proximal regulatory elements are necessary to attain some 20% of the full response and we suspect a role for sequences homologous to mammalian IL6 response elements and interferon-gamma responsive sites in this up-regulation. The transgenic experiments also reveal the existence of a distal regulatory element located upstream of -0.6 kb which increases the level of expression by a factor of five.},
keywords = {Animals, Anti-Infective Agents, Base Sequence, beta-Galactosidase, DNA Mutational Analysis, Female, Gene Expression Regulation, Genetic, Genetically Modified, Germ Cells, hoffmann, Insect Hormones, Insect Proteins, M3i, Male, Models, Nucleic Acid, Promoter Regions, Recombinant Fusion Proteins, reichhart, Repetitive Sequences, Transformation},
pubstate = {published},
tppubtype = {article}
}