An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors

Nucleic Acids Res. 2001 Sep 1;29(17):3495-505. doi: 10.1093/nar/29.17.3495.

Abstract

We have characterized a 700 bp enhancer element around -6 kb relative to the HNF4alpha1 transcription start. This element increases activity and confers glucocorticoid induction to a heterologous as well as the homologous promoters in differentiated hepatoma cells and is transactivated by HNF4alpha1, HNF4alpha7, HNF1alpha and HNF1beta in dedifferentiated hepatoma cells. A 240 bp sub-region conserves basal and hormone-induced enhancer activity. It contains HNF1, HNF4, HNF3 and C/EBP binding sites as shown by DNase I footprinting and electrophoretic mobility shift assays using nuclear extracts and/or recombinant HNF1alpha and HNF4alpha1. Mutation analyses showed that the HNF1 site is essential for HNF1alpha transactivation and is required for full basal enhancer activity, as is the C/EBP site. Glucocorticoid response element consensus sites which overlap the C/EBP, HNF4 and HNF3 sites are crucial for optimal hormonal induction. We present a model that accounts for weak expression of HNF4alpha1 in the embryonic liver and strong expression in the newborn/adult liver via the binding sites identified in the enhancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Binding Sites / genetics
  • CCAAT-Enhancer-Binding Protein-alpha / metabolism
  • Chloramphenicol O-Acetyltransferase / genetics
  • Chloramphenicol O-Acetyltransferase / metabolism
  • DNA-Binding Proteins / metabolism
  • Dexamethasone / pharmacology
  • Enhancer Elements, Genetic / genetics*
  • Enhancer Elements, Genetic / physiology
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology*
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 3-alpha
  • Hepatocyte Nuclear Factor 4
  • Liver / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Plasmids / genetics
  • Promoter Regions, Genetic / genetics*
  • Protein Binding
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics
  • Regulatory Sequences, Nucleic Acid / physiology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CCAAT-Enhancer-Binding Protein-alpha
  • DNA-Binding Proteins
  • Foxa1 protein, mouse
  • Glucocorticoids
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 3-alpha
  • Hepatocyte Nuclear Factor 4
  • Hnf1a protein, mouse
  • Hnf1b protein, mouse
  • Nuclear Proteins
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Tcfl4 protein, mouse
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta
  • Dexamethasone
  • Luciferases
  • Chloramphenicol O-Acetyltransferase

Associated data

  • GENBANK/AF320052