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Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination
Scott E Leblanc1, Rajini Srinivasan, Cinzia Ferri
1Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of Neurochemistry
|April 20, 2005
Summary
Peripheral nerve myelination by Schwann cells needs extensive lipid synthesis. This study reveals early growth response 2 (Egr2)/Krox20 and sterol regulatory element binding proteins (SREBPs) synergistically activate lipid biosynthesis genes during myelination.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Schwann cell myelination of peripheral nerves is a lipid-intensive process.
- The sterol regulatory element binding protein (SREBP) pathway regulates cholesterol and lipid biosynthesis.
- Early growth response 2 (Egr2)/Krox20 is a key transcription factor for peripheral nerve myelination.
Purpose of the Study:
- To investigate the transcriptional coordination between Egr2/Krox20 and the SREBP pathway during peripheral nerve myelination.
- To understand the role of SREBP transactivators in the myelination process.
Main Methods:
- Analysis of gene expression during sciatic nerve myelination.
- Investigating the regulatory relationship between Egr2/Krox20 and SREBP pathway components.
- Reporter assays to assess promoter activation of SREBP target genes.
Main Results:
- Significant induction of SREBP1, SREBP2, and their target genes during sciatic nerve myelination.
- Egr2/Krox20 does not directly regulate SREBP pathway component levels.
- Egr2/Krox20 and SREBP transactivators synergistically activate promoters of SREBP target genes.
Conclusions:
- SREBP transactivators are crucial regulators in the peripheral nerve myelination process.
- Egr2/Krox20 directly induces cholesterol and lipid biosynthesis genes as part of the myelination program, in conjunction with SREBP activity.