Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination.
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.
Leblanc
Scott E
SE
Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Srinivasan
Rajini
R
Ferri
Cinzia
C
Mager
Gennifer M
GM
Gillian-Daniel
Anne Lynn
AL
Wrabetz
Lawrence
L
Svaren
John
J
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*
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