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
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CCAAT-Enhancer-Binding Proteins / genetics
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CCAAT-Enhancer-Binding Proteins / physiology
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Cell Line
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Cholesterol / biosynthesis*
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Cholesterol / genetics*
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Drug Synergism
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Early Growth Response Protein 2
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Humans
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Knockout
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Mice, Transgenic
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Myelin Sheath / genetics
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Myelin Sheath / physiology*
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Nerve Fibers, Myelinated / physiology*
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Peripheral Nerves / physiology
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Sciatic Nerve / metabolism
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Sciatic Nerve / physiology*
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Sterol Regulatory Element Binding Protein 1
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Sterol Regulatory Element Binding Protein 2
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Transcription Factors / biosynthesis
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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EGR2 protein, human
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Early Growth Response Protein 2
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Egr2 protein, mouse
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SREBF1 protein, human
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SREBF2 protein, human
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Srebf1 protein, mouse
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Srebf2 protein, mouse
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Sterol Regulatory Element Binding Protein 1
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Sterol Regulatory Element Binding Protein 2
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Transcription Factors
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Cholesterol