TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
2021 | journal article
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TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
Moyon, S.; Frawley, R.; Marechal, D.; Huang, D.; Marshall-Phelps, K. L. H.; Kegel, L. & Bøstrand, S. M. K. et al. (2021)
Nature Communications, 12(1) art. 3359. DOI: https://doi.org/10.1038/s41467-021-23735-3
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- Authors
- Moyon, Sarah; Frawley, Rebecca; Marechal, Damien; Huang, Dennis; Marshall-Phelps, Katy L. H.; Kegel, Linde; Bøstrand, Sunniva M. K.; Sadowski, Boguslawa; Jiang, Yong-Hui; Lyons, David A.; Casaccia, Patrizia
- Abstract
- 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.
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. - Issue Date
- 2021
- Journal
- Nature Communications
- eISSN
- 2041-1723
- Language
- English