Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination
Open Access
- 16 March 2005
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 93 (3), 737-748
- https://doi.org/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.Keywords
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