title: TRIM28 represses transcription of endogenous retroviruses in neural progenitor cells.
abstract: TRIM28 is a corepressor that mediates transcriptional silencing by establishing local heterochromatin. Here, we show that deletion of TRIM28 in neural progenitor cells (NPCs) results in high-level expression of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. We find that NPCs use TRIM28-mediated histone modifications to dynamically regulate transcription and silencing of ERVs, which is in contrast to other somatic cell types using DNA methylation. We also show that derepression of ERVs influences transcriptional dynamics in NPCs through the activation of nearby genes and the expression of long noncoding RNAs. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Our results warrant future studies on the role of ERVs in the healthy and diseased brain.
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Liana
authors.initials: L
authors.lastname: Fasching
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Adamandia
authors.initials: A
authors.lastname: Kapopoulou
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sachdeva
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Petri
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Marie E
authors.initials: ME
authors.lastname: Jönsson
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Männe
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Turelli
authors.affiliation: Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden.
authors.forename: Patric
authors.initials: P
authors.lastname: Jern
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM, U896, Université Montpellier; Institut Régional du Cancer Montpellier, Montpellier 34298, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cammas
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.affiliation: Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden. Electronic address: johan.jakobsson@med.lu.se.
authors.forename: Johan
authors.initials: J
authors.lastname: Jakobsson
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000821:virology; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000472:pathogenicity; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism* / Q000821:virology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics*; D013234:Stem Cells / Q000378:metabolism / Q000821:virology; D014158:Transcription, Genetic; D000076183:Tripartite Motif-Containing Protein 28
chemical_list: D006570:Heterochromatin; D006657:Histones; D009687:Nuclear Proteins; D012097:Repressor Proteins; C103190:Trim28 protein, mouse; D000076183:Tripartite Motif-Containing Protein 28