Regulatory mechanisms for liver-selective transcription of genes for ornithine cycle enzymes

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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.