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

• Published in: Journal of neurochemistry Vol. 93; no. 3; pp. 737 - 748
• Main Authors: LeBlanc, Scott E., Srinivasan, Rajini, Ferri, Cinzia, Mager, Gennifer M., Gillian‐Daniel, Anne Lynn, Wrabetz, Lawrence, Svaren, John
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-05-2005; Blackwell
• Subjects: Animals; Biological and medical sciences; 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 2; Early Growth Response Protein 2; Fundamental and applied biological sciences. Psychology; Humans; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Mice, Transgenic; Molecular and cellular biology; Molecular genetics; Myelin Sheath - genetics; Myelin Sheath - physiology; myelination; Nerve Fibers, Myelinated - physiology; Peripheral Nerves - physiology; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Schwann; Sciatic Nerve - metabolism; Sciatic Nerve - physiology; sterol regulatory element binding protein; Sterol Regulatory Element Binding Protein 1; Sterol Regulatory Element Binding Protein 2; transcription; Transcription Factors - biosynthesis; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology; Transcription. Transcription factor. Splicing. Rna processing; Vertebrates: nervous system and sense organs; Peripheral nerve; sterol regulatory element binding protein; Program; Schwann; transcription; Growth; Induction; Neuroglia; Lipids; Biosynthesis; Gene expression; Cholesterol; Binding protein; Gene; Schwann cell; myelination; Sciatic nerve; early growth response 2
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03056.x

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.