TY - JOUR
T1 - Regulation of cholesterol/lipid biosynthetic genes by Egr2/Krox20 during peripheral nerve myelination
AU - LeBlanc, Scott E.
AU - Srinivasan, Rajini
AU - Ferri, Cinzia
AU - Mager, Gennifer M.
AU - Gillian-Daniel, Anne Lynn
AU - Wrabetz, Lawrence
AU - Svaren, John
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
KW - Early growth response 2
KW - Myelination
KW - Schwann
KW - Sterol regulatory element binding protein
KW - Transcription
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U2 - 10.1111/j.1471-4159.2005.03056.x
DO - 10.1111/j.1471-4159.2005.03056.x
M3 - Article
C2 - 15836632
AN - SCOPUS:18144430271
VL - 93
SP - 737
EP - 748
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 3
ER -