Nucleic Acids Research, Vol 25, Issue 12 2501-2508, Copyright © 1997 by Oxford University Press
GA Bulla
Hepatocyte nuclear factors-1alpha (HNF1alpha) and -4 (HNF4) are components
of a liver-enriched transcription activation pathway which is thought to
play a critical role in hepatocyte-specific gene expression, including
activation of alpha1-antitrypsin gene expression. HNF1alpha, HNF4 and
alpha1-antitrypsin (alpha1AT) genes are extinguished in hepatoma/fibroblast
somatic cell hybrids, suggesting that fibroblasts contain a repressor-like
activity. To determine the molecular basis for silencing of these genes in
cell hybrids, ectopic expression of HNF1alpha and HNF4 was used. Results
show that constitutive expression of HNF4 prevents extinction of HNF1alpha
gene expression in hepatoma/fibroblast hybrids. In contrast, forced
HNF1alpha expression failed to prevent extinction of the HNF4 locus in cell
hybrids. Likewise, the alpha1AT gene remained silent in the presence of
both HNF1alpha and HNF4. These results suggest that extinction of HNF1alpha
is a simple lack-of-activation phenotype, whereas extinction of HNF4
andalpha1AT loci is more complex, perhaps involving negative regulation.
ARTICLES
Hepatocyte nuclear factor-4 prevents silencing of hepatocyte nuclear factor-1 expression in hepatoma x fibroblast cell hybrids
Pediatric Research Institute, St Louis University Health Sciences Center and Cardinal Glennon Children's Hospital, 3662 Park Avenue, St Louis, MO 63110, USA. bullaga@sluvca.slu.edu
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