HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids.
Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.
Unité de Génétique de la Différenciation, URA Centre National de la Recherche Scientifique 1149, Institut Pasteur, Paris, France.
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G
Griffo
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C
Hamon-Benais
P O
PO
Angrand
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M
Fox
L
L
West
O
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Lecoq
S
S
Povey
D
D
Cassio
M
M
Weiss
D000418:Albumins / Q000235:genetics; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015152:Blotting, Northern; D002460:Cell Line; D002875:Chromosomes / Q000502:physiology*; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D005786:Gene Expression Regulation; 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; D016350:Leucine Zippers; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D009687:Nuclear Proteins; D010750:Phosphoproteins; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000418:Albumins; 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; C496489:Hnf1a protein, rat; C403128:MLX protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta