CCAAT/enhancer-binding protein beta (C/EBP beta) binds and activates while hepatocyte nuclear factor-4 (HNF-4) does not bind but represses the liver-type arginase promoter

Eur J Biochem. 1996 Mar 1;236(2):500-9. doi: 10.1111/j.1432-1033.1996.00500.x.


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/EBP beta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / genetics*
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation, Enzymologic*
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Liver / enzymology*
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / physiology*
  • Phosphoproteins / physiology*
  • Promoter Regions, Genetic*
  • Rats
  • Repressor Proteins / physiology*
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • Hepatocyte Nuclear Factor 4
  • MLX protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Repressor Proteins
  • Tcfl4 protein, mouse
  • Transcription Factors
  • Arginase