Selective loss of the hepatic phenotype due to the absence of a transcriptional activation pathway.
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.
Bulla
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GA
Department of Pediatrics, St. Louis University Health Sciences Center, Missouri, USA.
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002877:Chromosomes, Human / Q000235:genetics; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D006822:Hybrid Cells; D008099:Liver / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins; D010641:Phenotype; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C496487:HNF1A protein, human; C496495:HNF1B protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496488:Hnf1a protein, mouse; C496489:Hnf1a protein, rat; C496496:Hnf1b protein, mouse; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta