| Summary: | 碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 94 === sterol regulatory element binding proteins (SREBPs) are transcription factors involved in fatty acid and cholesterol biosynthesis. Three isoforms: SREBP-1a, SREBP-1c, and SREBP-2 are found in mammals. They can turn on the fatty acid and cholesterol biosynthesis by activating multiple genes like acetyl CoA carboxylase(ACC) and fatty acid synthase(FAS) relating to fatty acid biosynthesis and 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase, HMG CoA reductase, and squalene synthase relating to cholesterol biosynthesis. In mouse model, liver steatosis and enlarged liver by overexpressing SREBP-1 can be observed. In my study, I had cloned the full length zebrafish ( Danio rerio) SREBP1 (3540 bp) cDNA encoding 1105 amino acids and 3Kb promoter of zebrafish SREBP1 gene with two putative SREBP1 responsive elements (SRE) and one CCATT/enhancer binding protein (C/EBP) binding site. From the promoter assay of 3Kb zebrafish SREBP1 promoter, the transcription factors mature SREBP1, C/EBPα and C/EBPβ could activate the expression of SREBP1 gene at about 6, 3 and 4 folds, respectively whereas the hepatocyte nuclear factor 1α(HNF1α), 1β, and 1γ didn’t show significant transactivation activities. In addition to, zebrafish SREBP1 gene can be significantly induced by hepatotoxin thioacetamide (TAA) treatment at 3rd week in adult liver of green-fluorescent liver transgenic line and at 1st week in HCV-core protein transgenic line. Auto-activation of mature SREBP1 to SREBP1 gene in combination with C/EBP
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