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

Abstract

Liver-enrichedtrans-acting factors hepatocyte nuclear factor-1α (HNF1 α) 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→HNF1α pathway (1). In order to determine the influence of the HNF4→HNF1α 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.

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Bulla, G.A. Selective loss of the hepatic phenotype due to the absence of a transcriptional activation pathway. Somat Cell Mol Genet 23, 185–201 (1997). https://doi.org/10.1007/BF02721370

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  • DOI: https://doi.org/10.1007/BF02721370

Keywords

  • Variant Line
  • Hepatic Gene Expression
  • Variant Cell Line
  • Liver Gene Expression
  • Hepatic Phenotype