TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells
Liana Fasching,
Adamandia Kapopoulou,
Rohit Sachdeva,
Rebecca Petri,
Marie E. Jönsson,
Christian Männe,
Priscilla Turelli,
Patric Jern,
Florence Cammas,
Didier Trono,
Johan Jakobsson
Affiliations
Liana Fasching
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
Adamandia Kapopoulou
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Rohit Sachdeva
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
Rebecca Petri
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
Marie E. Jönsson
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
Christian Männe
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
Priscilla Turelli
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Patric Jern
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 751 23 Uppsala, Sweden
Florence Cammas
IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM, U896, Université Montpellier; Institut Régional du Cancer Montpellier, Montpellier 34298, France
Didier Trono
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
Johan Jakobsson
Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, Lund University, 221 84 Lund, Sweden
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.
