Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination
Open accessAbstract
The transcriptional control of CNS myelin gene expression is poorly understood. Here we identify gene model 98, which we have named myelin gene regulatory factor (MRF), as a transcriptional regulator required for CNS myelination. Within the CNS, MRF is specifically expressed by postmitotic oligodendrocytes. MRF is a nuclear protein containing an evolutionarily conserved DNA binding domain homologous to a yeast transcription factor. Knockdown of MRF in oligodendrocytes by RNA interference prevents expression of most CNS myelin genes; conversely, overexpression of MRF within cultured oligodendrocyte progenitors or the chick spinal cord promotes expression of myelin genes. In mice lacking MRF within the oligodendrocyte lineage, premyelinating oligodendrocytes are generated but display severe deficits in myelin gene expression and fail to myelinate. These mice display severe neurological abnormalities and die because of seizures during the third postnatal week. These findings establish MRF as a critical transcriptional regulator essential for oligodendrocyte maturation and CNS myelination.
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The proximal 300 bp human MAG promoter fragment contains evolutionarily conserved binding sites for MRF and RNF10.
“Finally, we also selected the proximal 300 bp fragment for further characterization as it contains evolutionary conserved binding sites for myelin gene regulatory factor (MRF) and Ring Finger Protein 10 (RNF10), critical activators of myelination in oligodendrocytes or Schwann cells, respectively (Hoshikawa et al., 2008; Emery et al., 2009; Bujalka et al., 2013).”
From Recombinant Human Myelin-Associated Glycoprotein Promoter Drives Selective AAV-Mediated Transgene Expression in Oligodendrocytes (2016) · cites this paper as Emery et al., 2009
The Discussion (page unavailable) identifies MRF as a regulator required for oligodendrocyte maturation and CNS myelination. It does not establish that the proximal 300 bp human MAG promoter contains conserved MRF or RNF10 binding sites; the binding-site claim is unsupported by this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCell type-specific transcription factor expression is important for cell fate determination and cell differentiation.
“Cell type-specific transcription factor expression is important for cell fate determination and cell differentiation (e.g., Neu-roD for specification of neuron cell fate, Olig2 for specification of oligodendrocyte fate, and GM98/Myrf for oligodendrocyte differentiation; Lee et al., 1995;Zhou and Anderson, 2002;Emery et al., 2009).”
From An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014) · cites this paper as Emery et al., 2009
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- Authors
- Emery, B., Agalliu, D., Cahoy, J. D., Watkins, T. A., Dugas, J. C., Mulinyawe, S. B., Ibrahim, A., Ligon, K. L., Rowitch, D. H., & Barres, B. A.
- Affiliations
- Stanford Medicine (US)
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Emery, Ben
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 138
- Issue
- 1
- Pages
- 172-185
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2757090
- OpenAlex
- W2062403533
- Cited by
- 559
- References
- 27
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 45 · 2023: 46 · 2022: 26 · 2021: 53 · 2020: 45 · 2019: 36 · 2018: 38 · 2017: 37 · 2016: 24 · 2015: 25 · 2014: 27 · 2013: 32 · 2012: 17
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1477 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (R01EY010257, R01 EY10257)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CNS myelination, transcriptional regulation, oligodendrocytes, myelin gene expression, oligodendrocyte maturation, oligodendrocyte progenitors, DNA-binding domain, RNAi knockdown, knockout mice, neurological abnormalities, seizures
- MeSH terms
- Animals, Brain, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Myelin Sheath, Neurons, Oligodendroglia, Transcription Factors, Mice
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