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

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Somatic Cell and Molecular Genetics

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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Authors and Affiliations

  1. Department of Pediatrics, Pediatric Research Institute, St. Louis University Health Sciences Center, 3662 Park Avenue, 63110, St. Louis, Missouri

    Gary A. Bulla

  2. Cardinal Glennon Children’s Hospital, 3662 Park Avenue, 63110, St. Louis, Missouri

    Gary A. Bulla

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  1. Gary A. Bulla
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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

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