title: Interplay of TRIM28 and DNA methylation in controlling human endogenous retroelements.
abstract: Reverse transcription-derived sequences account for at least half of the human genome. Although these retroelements are formidable motors of evolution, they can occasionally cause disease, and accordingly are inactivated during early embryogenesis through epigenetic mechanisms. In the mouse, at least for endogenous retroviruses, important mediators of this process are the tetrapod-specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is responsible for controlling a very broad range of human-specific endogenous retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a consequence, a marked effect on the transcriptional dynamics of these cells. It further reveals reciprocal dependence between TRIM28 recruitment at specific families of EREs and DNA methylation. It finally points to the importance of persistent TRIM28-mediated control of ERE transcriptional impact beyond their presumed inactivation by DNA methylation.
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Nathaly
authors.initials: N
authors.lastname: Castro-Diaz
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Flavia
authors.initials: F
authors.lastname: Marzetta
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Adamandia
authors.initials: A
authors.lastname: Kapopoulou
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Charlène
authors.initials: C
authors.lastname: Raclot
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Julien
authors.initials: J
authors.lastname: Duc
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Vannary
authors.initials: V
authors.lastname: Tieng
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
authors.forename: Simon
authors.initials: S
authors.lastname: Quenneville
authors.affiliation: School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland; didier.trono@epfl.ch.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
mesh_terms: D020087:Alu Elements; D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D053595:Embryonic Stem Cells; D020077:Endogenous Retroviruses / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D012097:Repressor Proteins / Q000502:physiology*; D014158:Transcription, Genetic; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D012097:Repressor Proteins; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28