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TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice

Author

Listed:
  • Sarah Moyon

    (Neuroscience Initiative Advanced Science Research Center)

  • Rebecca Frawley

    (Neuroscience Initiative Advanced Science Research Center)

  • Damien Marechal

    (Neuroscience Initiative Advanced Science Research Center)

  • Dennis Huang

    (Neuroscience Initiative Advanced Science Research Center)

  • Katy L. H. Marshall-Phelps

    (Centre for Discovery Brain Sciences)

  • Linde Kegel

    (Centre for Discovery Brain Sciences)

  • Sunniva M. K. Bøstrand

    (Centre for Discovery Brain Sciences)

  • Boguslawa Sadowski

    (Department of Neurogenetics
    Max-Planck-Institute of Experimental Medicine
    Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB))

  • Yong-Hui Jiang

    (Duke University School of Medicine)

  • David A. Lyons

    (Centre for Discovery Brain Sciences)

  • Wiebke Möbius

    (Department of Neurogenetics
    Max-Planck-Institute of Experimental Medicine
    Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB))

  • Patrizia Casaccia

    (Neuroscience Initiative Advanced Science Research Center
    The Graduate Center of The City University of New York)

Abstract

The mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven-Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions. DNA hydroxymethylation and transcriptomic analyses identify TET1-target in adult oligodendrocytes, as genes regulating neuro-glial communication, including the solute carrier (Slc) gene family. Among them, we show that the expression levels of the Na+/K+/Cl− transporter, SLC12A2, are higher in Tet1 overexpressing cells and lower in old or Tet1 knockout. Both aged mice and Tet1 mutants also present inefficient myelin repair and axo-myelinic swellings. Zebrafish mutants for slc12a2b also display swellings of CNS myelinated axons. Our findings suggest that TET1 is required for adult myelin repair and regulation of the axon-myelin interface.

Suggested Citation

  • Sarah Moyon & Rebecca Frawley & Damien Marechal & Dennis Huang & Katy L. H. Marshall-Phelps & Linde Kegel & Sunniva M. K. Bøstrand & Boguslawa Sadowski & Yong-Hui Jiang & David A. Lyons & Wiebke Möbiu, 2021. "TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23735-3
    DOI: 10.1038/s41467-021-23735-3
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    Cited by:

    1. John N. Mariani & Benjamin Mansky & Pernille M. Madsen & Dennis Salinas & Deniz Kesmen & Nguyen P. T. Huynh & Nicholas J. Kuypers & Erin R. Kesel & Janna Bates & Casey Payne & Devin Chandler-Militello, 2024. "Repression of developmental transcription factor networks triggers aging-associated gene expression in human glial progenitor cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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