1994 Fiscal Year Final Research Report Summary
Regulatory mechanisms for liver-selective transcription of genes for ornithine cycle enzymes
| Project/Area Number |
05670130
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKIGUCHI Masaki Kumamoto University, School of Medicine Associate Professor, 医学部, 助教授 (40179578)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Transcriptional regulation / Liver / Ornithine cycle / Arginase / Promoter / HNF-4 / COUP-TF / C / EBP |
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| Research Abstract |
To clarify control mechanisms of tissue-specific transcription, we have investigated regulatory regions of genes for ornithine cycle enzymens that are expressed liver-specifically. Peculiarly at a glance, the promoter of arginase, the last enzyme of the cycle, was stimulated by a ubiquitous member of the steroid receptor superfamily COUP-TF,while it was repressed by a liver-selective member HNF-4. A tempting speculation is that HNF-4 is involved in repression of the arginase gene specifically in tissues such as the small intestine and kidney where HNF-4 is expressed but arginase is not expressed. Here, I investigated a COUP-TF/HNF-4-responsive element(s) in the arginase promoter. Using transient transfection system with a hepatoma cell line HepG2, a COUP-TF-responsive element was identified in the region around the position -50 bp of the trascription start site. However, this region did not bind with COUP-TF nor HNF-4.On the other hand, this region did bind with members of the C/EBP family, and functioned as an element responsible for activation of the promoter by the members. One posibility is that COUP-TF and HNF-4 regulate the arginase promoter through interaction with factors such as C/EBPbeta without directly binding to the arginase promoter.
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