期刊
JOURNAL OF NEUROCHEMISTRY
卷 93, 期 3, 页码 737-748出版社
WILEY
DOI: 10.1111/j.1471-4159.2005.03056.x
关键词
early growth response 2; myelination; Schwann; sterol regulatory element binding protein; transcription
资金
- NHLBI NIH HHS [T32 HL007654] Funding Source: Medline
- NICHD NIH HHS [P30HD03352, HD41590, R01 HD041590] Funding Source: Medline
- PHS HHS [T32 G08688] Funding Source: Medline
- Telethon [GGP030074] Funding Source: Medline
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.
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