Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination

Scott E. LeBlanc, Rajini Srinivasan, Cinzia Ferri, Gennifer M. Mager, Anne Lynn Gillian-Daniel, Lawrence Wrabetz, John Svaren

Research output: Contribution to journalArticlepeer-review

Abstract

Myelination of peripheral nerves by Schwann cells requires a large amount of lipid and cholesterol biosynthesis. To understand the transcriptional coordination of the myelination process, we have investigated the developmental relationship between early growth response 2 (Egr2)/Krox20 - a pivotal regulator of peripheral nerve myelination - and the sterol regulatory element binding protein (SREBP) pathway, which controls expression of cholesterol/lipid biosynthetic genes. During myelination of sciatic nerve, there is a very significant induction of SREBP1 and SREBP2, as well as their target genes, suggesting that the SREBP transactivators are important regulators in the myelination process. Egr2/Krox20 does not appear to directly regulate the levels of SREBP pathway components, but rather, we found that Egr2/Krox20 and SREBP transactivators can synergistically activate promoters of several SREBP target genes, indicating that direct induction of cholesterol/lipid biosynthetic genes by Egr2/ Krox20 is a part of the myelination program regulated by this transactivator.

Original languageEnglish
Pages (from-to)737-748
Number of pages12
JournalJournal of Neurochemistry
Volume93
Issue number3
DOIs
Publication statusPublished - May 2005

Keywords

  • Early growth response 2
  • Myelination
  • Schwann
  • Sterol regulatory element binding protein
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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