Multiple elements for negative regulation of the rat catalase gene expression in dedifferentiated hepatoma cells

Like such hepatic genes as those for albumin and aldolase B, the rat catala se gene shows markedly reduced expression in carcinogenesis of hepatocytes, Strong silencer activity has been widely observed in the 5'-flanking regio n of the gene, downstream from the G-rich sequence identified in a previous study. In this study, we identified and characterized multiple elements in volved in negative regulation of catalase gene expression by reporter assay and gel shift assay. One of the silencer elements is located 3 kb upstream of the gene and has GATATCCCGATATC as core sequence. The observation that protein binding to the element is abundantly expressed in dedifferentiated hepatoma cell lines, but scarcely in well-differentiated cell lines suggest s that this element is involved in negative regulation of the catalase gene expression in hepatocarcinogenesis. This element was targeted by a novel 2 0-kDa nuclear protein, which is designated HNRF (hepatocarcinogenesis-relat ed negative regulatory factor).