Postnatal liver-specific expression of human insulin-like growth factor-II is highly stimulated by the transcriptional activators liver-enriched activating protein and CCAAT/enhancer binding protein-alpha

Mol Endocrinol. 1995 Apr;9(4):424-34. doi: 10.1210/mend.9.4.7659086.


Transcription of the human gene encoding insulin-like growth factor II (IGF-II) is directed by four promoters (P1-P4), which are active in a tissue- and development-dependent manner. High levels of IGF-II in postnatal serum are due to activation of P1 in the liver. Since liver tissue contains high levels of the bZIP factors, liver-enriched activating protein (LAP), the CCAAT/enhancer binding protein-alpha (C/EBP alpha), and the D-element binding protein (DBP), and since P1 contains a functional C/EBP alpha binding site (P1 CBS), we have examined the role of these transcription factors in the activation of IGF-II P1. Transient transfection experiments reveal that P1 can be activated up to 15-fold by LAP and up to 6-fold by C/EBP alpha but can not be activated by DBP. Electrophoretic mobility shift assays with liver nuclear extract show that P1 CBS is predominantly bound by LAP and C/EBP alpha. Mutational analysis of P1 CBS indicates that DBP binding is prevented by one distinct G-C base pair in the P1 CBS element. The P1 CBS element is a high affinity binding site, which was demonstrated by comparing P1 CBS with other LAP-C/EBP alpha binding sites employing quantitative electrophoretic mobility shift assay. These results indicate that LAP and C/EBP alpha are major contributors to the postnatal liver-specific activation of the human IGF-II promoter P1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Proteins
  • Carcinoma, Hepatocellular / pathology
  • DNA-Binding Proteins / pharmacology*
  • Gene Expression Regulation, Developmental / drug effects*
  • HeLa Cells / drug effects
  • Humans
  • Insulin-Like Growth Factor II / biosynthesis*
  • Insulin-Like Growth Factor II / genetics
  • Liver / growth & development
  • Liver / metabolism*
  • Liver Neoplasms / pathology
  • Molecular Sequence Data
  • Nuclear Proteins / pharmacology*
  • Promoter Regions, Genetic / drug effects
  • Protein Binding
  • Recombinant Fusion Proteins / biosynthesis
  • Regulatory Sequences, Nucleic Acid*
  • Repressor Proteins / pharmacology
  • Transcription Factors / pharmacology
  • Transcription, Genetic / drug effects*
  • Tumor Cells, Cultured / drug effects


  • CCAAT-Enhancer-Binding Protein-beta
  • CCAAT-Enhancer-Binding Proteins
  • DBP protein, human
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • Insulin-Like Growth Factor II