title: Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination.
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.
authors.affiliation: Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Leblanc
authors.forename: Rajini
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ferri
authors.forename: Gennifer M
authors.initials: GM
authors.lastname: Mager
authors.forename: Anne Lynn
authors.initials: AL
authors.lastname: Gillian-Daniel
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wrabetz
authors.forename: John
authors.initials: J
authors.lastname: Svaren
mesh_terms: D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004357:Drug Synergism; D051767:Early Growth Response Protein 2; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000235:genetics / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology; D012584:Sciatic Nerve / Q000378:metabolism / Q000502:physiology*; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C497326:EGR2 protein, human; D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; C497388:Srebf1 protein, mouse; C497391:Srebf2 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors; D002784:Cholesterol