The Transcription Factors Sox10 and Myrf Define an Essential Regulatory Network Module in Differentiating Oligodendrocytes
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Myelin is essential for rapid saltatory conduction and is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In both cell types the transcription factor Sox10 is an essential component of the myelin-specific regulatory network. Here we identify Myrf as an oligodendrocyte-specific target of Sox10 and map a Sox10 responsive enhancer to an evolutionarily conserved element in intron 1 of the Myrf gene. Once induced, Myrf cooperates with Sox10 to implement the myelination program as evident from the physical interaction between both proteins and the synergistic activation of several myelin-specific genes. This is strongly reminiscent of the situation in Schwann cells where Sox10 first induces and then cooperates with Krox20 during myelination. Our analyses indicate that the regulatory network for myelination in oligodendrocytes is organized along similar general principles as the one in Schwann cells, but is differentially implemented.
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This transition was accompanied by reduced activity of myelin-associated gene networks and diminished regulon activity of key transcriptional regulators, including MYRF and NKX6-2, which serve as central regulators of myelin gene expression programs.
“This transition was accompanied by reduced activity of myelin-associated gene networks and diminished regulon activity of key transcriptional regulators, including MYRF and NKX6-2, which serve as central regulators of myelin gene expression programs (53-55) (Fig. 5J).”
From Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex (2026) · cites this paper as [54]
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- Authors
- Hornig, J., Fröb, F., Vogl, M. R., Hermans-Borgmeyer, I., Tamm, E. R., & Wegner, M.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Regensburg (DE)
- Corresponding author
- Wegner, Michael
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-10-31
- Volume
- 9
- Issue
- 10
- Pages
- e1003907
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3814293
- OpenAlex
- W2083561210
- Cited by
- 228
- References
- 47
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 19 · 2023: 11 · 2022: 24 · 2021: 19 · 2020: 23 · 2019: 24 · 2018: 16 · 2017: 16 · 2016: 17 · 2015: 14 · 2014: 5 · 2013: 3
- FWCI
- 4.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (We1326/11)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SOX10, MYRF, oligodendrocyte differentiation, myelination, transcriptional regulatory networks, enhancers, Krox20, Schwann cells, protein-protein interaction, central nervous system myelin
- MeSH terms
- Animals, Cell Differentiation, Cell Line, Central Nervous System, High Mobility Group Proteins, Humans, Mice, Transgenic, Myelin Sheath, Oligodendroglia, Schwann Cells, Transcription Factors, Gene Expression Regulation, Developmental, Mice, Early Growth Response Protein 2, Gene Regulatory Networks, SOXE Transcription Factors
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