title: TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells.
abstract: TRIM28 is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact of this process is the protection of cellular gene expression in early embryos from perturbation by cis-acting activators contained within these retroelements. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced by histone modifications typical of active enhancers, stimulating transcription of nearby cellular genes, notably those harboring bivalent promoters. Correspondingly, ERV-derived sequences can repress or enhance expression from an adjacent promoter in transgenic embryos depending on their TRIM28 sensitivity in ES cells. TRIM28-mediated control of ERVs is therefore crucial not just to prevent retrotransposition, but more broadly to safeguard the transcriptional dynamics of early embryos.
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Rowe
authors.forename: Adamandia
authors.initials: A
authors.lastname: Kapopoulou
authors.forename: Andrea
authors.initials: A
authors.lastname: Corsinotti
authors.forename: Liana
authors.initials: L
authors.lastname: Fasching
authors.forename: Todd S
authors.initials: TS
authors.lastname: Macfarlan
authors.forename: Yara
authors.initials: Y
authors.lastname: Tarabay
authors.forename: Stéphane
authors.initials: S
authors.lastname: Viville
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Pfaff
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D056426:Genetic Loci; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic; D000076183:Tripartite Motif-Containing Protein 28; D015854:Up-Regulation
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; D012097:Repressor Proteins; D018626:Retroelements; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28