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

229 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Regulator Genes
Myelin Sheath
Genes
Oligodendroglia
Gene Expression
Gene expression
Gene Knockdown Techniques
Nuclear Proteins
RNA Interference
Yeast
Spinal Cord
Seizures
Transcription Factors
Yeasts
RNA
DNA

Keywords

  • HUMDISEASE
  • MOLNEURO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Emery, B., Agalliu, D., Cahoy, J. D., Watkins, T. A., Dugas, J. C., Mulinyawe, S. B., ... 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

Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination. / Emery, Ben; Agalliu, Dritan; Cahoy, John D.; Watkins, Trent A.; Dugas, Jason C.; Mulinyawe, Sara B.; Ibrahim, Adilijan; Ligon, Keith L.; Rowitch, David H.; Barres, Ben A.

In: Cell, Vol. 138, No. 1, 10.07.2009, p. 172-185.

Research output: Contribution to journalArticle

Emery, B, Agalliu, D, Cahoy, JD, Watkins, TA, Dugas, JC, Mulinyawe, SB, Ibrahim, A, Ligon, KL, Rowitch, DH & Barres, BA 2009, 'Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination', Cell, vol. 138, no. 1, pp. 172-185. https://doi.org/10.1016/j.cell.2009.04.031
Emery, Ben ; Agalliu, Dritan ; Cahoy, John D. ; Watkins, Trent A. ; Dugas, Jason C. ; Mulinyawe, Sara B. ; Ibrahim, Adilijan ; Ligon, Keith L. ; Rowitch, David H. ; Barres, Ben A. / Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS Myelination. In: Cell. 2009 ; Vol. 138, No. 1. pp. 172-185.
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