Selective loss of the hepatic phenotype due to the absence of a transcriptional activation pathway

Somat Cell Mol Genet. 1997 May;23(3):185-201. doi: 10.1007/BF02721370.

Abstract

Liver-enriched trans-acting factors hepatocyte nuclear factor-1 alpha (HNF1 alpha) and -4 (HNF4) are components of a transcriptional activation pathway that is thought to play a major role in hepatic gene activation. We previously described the isolation and characterization of distinct classes of hepatoma variants which lack the HNF4-->HNF1 alpha pathway (1). In order to determine the influence of the HNF4-->HNF1 alpha pathway on hepatic gene expression, genetic rescue experiments were done using hepatoma variant line H11 as a model system. Results suggest that this pathway is required for basal expression of a number of endogenous hepatocyte-specific genes. Complementation groups were established by fusion of H11 cells with other variant lines. Lastly, introduction of human chromosome 20 (containing the HNF4 locus) or randomly-marked human chromosomes into H11 cells failed to rescue the hepatic phenotype, suggesting that what appears to be a 'simple' defect may involve multiple genetic loci.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Carcinoma, Hepatocellular
  • Cell Line
  • Chromosomes, Human / genetics
  • DNA-Binding Proteins*
  • Fibroblasts
  • Gene Expression Regulation*
  • Gene Transfer Techniques
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Hepatocyte Nuclear Factor 4
  • Humans
  • Hybrid Cells
  • Liver / metabolism*
  • Mice
  • Nuclear Proteins*
  • Phenotype
  • Phosphoproteins / biosynthesis
  • Phosphoproteins / genetics
  • Rats
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription Factors / physiology
  • Transcription, Genetic*
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Binding Proteins
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 4
  • Hnf1a protein, mouse
  • Hnf1a protein, rat
  • Hnf1b protein, mouse
  • MLX protein, human
  • Nuclear Proteins
  • Phosphoproteins
  • Tcfl4 protein, mouse
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta