Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination

Ben Emery, Dritan Agalliu, John D. Cahoy, Trent A. Watkins, Jason C. Dugas, Sara B. Mulinyawe, Adilijan Ibrahim, Keith L. Ligon, David H. Rowitch, Ben A. Barres

Research output: Contribution to journalArticle

254 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)172-185
Number of pages14
JournalCell
Volume138
Issue number1
DOIs
StatePublished - Jul 10 2009

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    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. (2009). Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination. Cell, 138(1), 172-185. https://doi.org/10.1016/j.cell.2009.04.031