Multiple Elements for Negative Regulation of the Rat Catalase Gene Expression in Dedifferentiated Hepatoma Cells

• Published in: Journal of biochemistry (Tokyo) Vol. 128; no. 6; pp. 1025 - 1031
• Main Authors: Takeuchi, Toshiyuki, Nakamura, Seiichi, Kayasuga, Atsushi, Isa, Shun-ichi, Sato, Kenzo
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-12-2000
• Subjects: Animals; Base Sequence; Catalase - genetics; catalase gene; Cell Differentiation; Cell Transformation, Neoplastic - genetics; core sequence; DNA; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; hepatocarcinogenesis; Liver Neoplasms, Experimental - enzymology; Liver Neoplasms, Experimental - pathology; Rats; Regulatory Sequences, Nucleic Acid; silencer; Transcription, Genetic; transcriptional regulation
• ISSN: 0021-924X
• DOI: 10.1093/oxfordjournals.jbchem.a022830

Like such hepatic genes as those for albumin and aldolase B, the rat catalase gene shows markedly reduced expression in carcinogenesis of hepatocytes. Strong silencer activity has been widely observed in the 5′-flanking region of the gene, downstream from the G-rich sequence identified in a previous study. In this study, we identified and characterized multiple elements involved 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 suggests that this element is involved in negative regulation of the catalase gene expression in hepatocar-cinogenesis. This element was targeted by a novel 20-kDa nuclear protein, which is designated HNRF (hepatocarcinogenesis-related negative regulatory factor).