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

J Neurochem. 2005 May;93(3):737-48. doi: 10.1111/j.1471-4159.2005.03056.x.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / physiology
  • Cell Line
  • Cholesterol / biosynthesis*
  • Cholesterol / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Drug Synergism
  • Early Growth Response Protein 2
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Knockout
  • Mice, Transgenic
  • Myelin Sheath / genetics
  • Myelin Sheath / physiology*
  • Nerve Fibers, Myelinated / physiology*
  • Peripheral Nerves / physiology
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / physiology*
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors / biosynthesis
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • SREBF1 protein, human
  • SREBF2 protein, human
  • Srebf1 protein, mouse
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Transcription Factors
  • Cholesterol