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EEF1A1 deacetylation enables transcriptional activation of remyelination

  • Duman, Mert Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany
  • Vaquié, Adrien Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Nocera, Gianluigi Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany
  • Heller, Manfred Proteomics and Mass Spectrometry Core Facility, Department for BioMedical Research, University of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland
  • Stumpe, Michael Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Sankar, Devanarayanan Siva Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Dengjel, Jörn Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Meijer, Dies Center for Discovery Brain Sciences, Edinburgh Medical School, University of Edinburgh, 15 George Square, Edinburgh EH8 9XD, United Kingdom
  • Yamaguchi, Teppei FMI for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, 4058 Basel, Switzerland
  • Matthias, Patrick FMI for Biomedical Research, Novartis Research Foundation, Maulbeerstrasse 66, 4058 Basel, Switzerland
  • Zeis, Thomas Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
  • Schaeren-Wiemers, Nicole Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland
  • Hayoz, Antoinette Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Ruff, Sophie Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland
  • Jacob, Claire Department of Biology, University of Fribourg, Chemin du Musée 10, 1700, Fribourg, Switzerland - Department of Biology, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 15, 55128 Mainz, Germany
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    09.07.2020
Published in:
  • Nature Communications. - 2020, vol. 11, no. 1, p. 3420
English Remyelination of the peripheral and central nervous systems (PNS and CNS, respectively) is a prerequisite for functional recovery after lesion. However, this process is not always optimal and becomes inefficient in the course of multiple sclerosis. Here we show that, when acetylated, eukaryotic elongation factor 1A1 (eEF1A1) negatively regulates PNS and CNS remyelination. Acetylated eEF1A1 (Ac- eEF1A1) translocates into the nucleus of myelinating cells where it binds to Sox10, a key transcription factor for PNS and CNS myelination and remyelination, to drag Sox10 out of the nucleus. We show that the lysine acetyltransferase Tip60 acetylates eEF1A1, whereas the histone deacetylase HDAC2 deacetylates eEF1A1. Promoting eEF1A1 deacetylation maintains the activation of Sox10 target genes and increases PNS and CNS remyelination efficiency. Taken together, these data identify a major mechanism of Sox10 regulation, which appears promising for future translational studies on PNS and CNS remyelination.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biology
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/308897
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