Competition between transcription factors HNF1 and HNF3, and alternative cell-specific activation by DBP and C/EBP contribute to the regulation of the liver-specific aldolase B promoter

Nucleic Acids Res. 1993 Feb 25;21(4):897-903. doi: 10.1093/nar/21.4.897.


The aldolase B proximal promoter is controlled by at least five elements spanning from -190 to -103 bp with respect to the start site of transcription. From 5' to 3', we found: a negative DE element, an activating C/EBP-DBP binding site, a CCAAT box binding NFY that seems to play a negative role, and an activating element consisting of two overlapping binding sites for HNF-1 and HNF-3. Contransfection experiments of aldolase B/CAT constructs and of expression vectors for different transcription factors were carried out in human hepatoma Hep G2 cells. We found that DBP and HNF-1 are strong transactivators of the aldolase B promoter while C/EBP and vHNF-1 are only weak activators and HNF-3 alone does not modify such activity. Deletion of the distal negative element results in a similar transactivation by C/EBP and DBP, enhanced for the former and reduced for the latter. In hepatocytes in primary culture, the strong transactivator is C/EBP while DBP is essentially inactive. This tissue-specificity of C/EBP and DBP action could depend on interaction with tissue-specific proteins bound to a neighbouring site, probably DE. Finally, HNF3 behaves as a very strong anti-activator of the aldolase B promoter. It competitively antagonizes transactivation by HNF-1 and non-competitively transactivation by DBP. This negative effect of HNF-3 and tissue-specificity of the transactivation potential of DBP and C/EBP are unique features of the aldolase B promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Binding, Competitive
  • CCAAT-Enhancer-Binding Proteins
  • Carcinoma, Hepatocellular
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism*
  • Fructose-Bisphosphate Aldolase / genetics*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Liver
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Organ Specificity
  • Promoter Regions, Genetic / physiology
  • Rats
  • Regulatory Sequences, Nucleic Acid / physiology
  • Trans-Activators
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • CCAAT-Enhancer-Binding Proteins
  • DBP protein, human
  • DBP protein, rat
  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hnf1a protein, rat
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Fructose-Bisphosphate Aldolase