Open AccessCCAAT/Enhancer‐Binding Protein β (C/EBPβ) Binds and Activates While Hepatocyte Nuclear Factor‐4 (HNF‐4) does not Bind but Represses the Liver‐Type Arginase Promoter
Author(s) -
Chowdhury Shoaib,
Gotoh Tomomi,
Mori Masataka,
Takiguchi Masaki
Publication year - 1996
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1996.00500.x
Subject(s) - microbiology and biotechnology , enhancer , transcription factor , ccaat enhancer binding proteins , promoter , biology , binding site , arginase , caat box , response element , hepatocyte nuclear factors , hepatocyte nuclear factor 4 , nuclear protein , gene , gene expression , biochemistry , nuclear receptor , amino acid , arginine
In an attempt to elucidate the mechanism governing liver‐specific transcription of the arginase gene, we previously detected two protein‐binding sites designated footprint areas A and B at positions around –90 and –55 bp, respectively, relative to the transcription start site of the rat arginase gene. Based on the finding that area A was bound by a liver‐selective factor(s) related to CCAAT/enhancer‐binding protein (C/EBP), we performed cotransfection assay and showed that C/EBP family members and a related factor, albumin D‐element‐binding protein (DBP) stimulate transcription from the arginase promoter. In addition to area A, a recombinant C/EBPβ protein bound to area B, which appeared to be primarily responsible for activation by C/EBPs. We unexpectedly found that the arginase promoter activity stimulated by C/EBPs and DBP was repressed by another liver‐enriched transcription factor, hepatocyte nuclear factor‐4 (HNF‐4). Analysis of chimeras formed between the arginase promoter and the herpes simplex virus thymidine kinase promoter allowed us to delimit the negative HNF‐4‐responsive element into the region overlapping with footprint area B. However, no apparent binding of HNF‐4 was observed in this negative element. We speculate that HNF‐4 is involved in fine regulation of the arginase gene in the liver or shutdown of the gene in nonhepatic tissues without direct binding to the promoter region.