PUBLICATION
TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice
- Authors
- Moyon, S., Frawley, R., Marechal, D., Huang, D., Marshall-Phelps, K.L.H., Kegel, L., Bøstrand, S.M.K., Sadowski, B., Jiang, Y.H., Lyons, D.A., Möbius, W., Casaccia, P.
- ID
- ZDB-PUB-210609-4
- Date
- 2021
- Source
- Nature communications 12: 3359 (Journal)
- Registered Authors
- Kegel, Linde, Lyons, David A.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cells, Cultured
- DNA Methylation*
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/metabolism
- Gene Expression Profiling/methods*
- Mice, Knockout
- Mice, Transgenic
- Mutation
- Myelin Sheath/genetics*
- Myelin Sheath/metabolism
- Oligodendroglia/cytology
- Oligodendroglia/metabolism
- Proto-Oncogene Proteins/genetics*
- Proto-Oncogene Proteins/metabolism
- RNA-Seq/methods
- Remyelination/genetics*
- Solute Carrier Family 12, Member 2/genetics
- Solute Carrier Family 12, Member 2/metabolism
- Zebrafish/genetics
- PubMed
- 34099715 Full text @ Nat. Commun.
Citation
Moyon, S., Frawley, R., Marechal, D., Huang, D., Marshall-Phelps, K.L.H., Kegel, L., Bøstrand, S.M.K., Sadowski, B., Jiang, Y.H., Lyons, D.A., Möbius, W., Casaccia, P. (2021) TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice. Nature communications. 12:3359.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping