PMID: 9171105Jun 15, 1997Paper

Hepatocyte nuclear factor-4 prevents silencing of hepatocyte nuclear factor-1 expression in hepatoma x fibroblast cell hybrids

Nucleic Acids Research
G A Bulla

Abstract

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.

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Citations

Feb 8, 2000·The International Journal of Biochemistry & Cell Biology·S MassaP Matthias
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·P Rollini, R E Fournier
Oct 5, 2001·Molecular and Cellular Biology·P Hatzis, I Talianidis
Apr 2, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Natalia L LazarevichStephen A Duncan
May 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Alistair J WattStephen A Duncan
Aug 15, 2006·Experimental and Molecular Pathology·Yana SupriatnaHiroshi Ishikura
Jun 5, 2012·Genomics·Gary A BullaArnold B Estanda
Sep 15, 2005·Bioscience Reports·Gary A Bulla, David M Kraus
Dec 20, 2002·Mechanisms of Development·Stephen A Duncan
Aug 31, 2010·Genomics·Gary A BullaSharon Hickman
Apr 15, 1999·Seminars in Cancer Biology·G I Abelev, T L Eraiser
Jan 18, 2005·The Biochemical Journal·Judith MagenheimJacob Bar-Tana

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