TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells

  1. Didier Trono1,6
  1. 1School of Life Sciences and Frontiers in Genetics Program, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
  2. 2Swiss Bioinformatics Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland;
  3. 3Wallenberg Neuroscience Center, Lund University, BMC A11, 221 84 Lund, Sweden;
  4. 4Gene Expression Laboratory and the Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA;
  5. 5Institute of Genetics and Molecular and Cellular Biology (IGBMC), University of Strasbourg, BP10142, Illkirch Cedex, France

    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.

    Footnotes

    • Received August 10, 2012.
    • Accepted December 6, 2012.

    This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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    1. Published in Advance December 10, 2012, doi: 10.1101/gr.147678.112 Genome Res. 23: 452-461 © 2013, Published by Cold Spring Harbor Laboratory Press

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