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- Title
Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination.
- Authors
LeBlanc, Scott E.; Srinivasan, Rajini; Ferri, Cinzia; Mager, Gennifer M.; Gillian-Daniel, Anne Lynn; Wrabetz, Lawrence; Svaren, John
- 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.
- Subjects
MYELINATION; PERIPHERAL nervous system; BIOSYNTHESIS; GENES; CHOLESTEROL; LIPIDS; HEREDITY; NERVOUS system; BIOCHEMISTRY
- Publication
Journal of Neurochemistry, 2005, Vol 93, Issue 3, p737
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2005.03056.x