ArticleMolecular and cellular biology1997
Hepatocyte nuclear factor 4 expression overcomes repression of the hepatic phenotype in dedifferentiated hepatoma cells.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 112 citations in OpenAlex.
- Evaluation of Protein Kinase cAMP-Activated Catalytic Subunit Alpha as a Therapeutic Target for Fibrolamellar Carcinoma.Gastro hep advances · 2023Article
- Hepatocellular Carcinoma Differentiation: Research Progress in Mechanism and Treatment.Frontiers in oncology · 2021Review
- Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis.Nature communications · 2019Article
- Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: the role of PGC1 coactivators.Nature reviews. Gastroenterology & hepatology · 2019Review
- Novel mechanisms of regulation of the expression and transcriptional activity of hepatocyte nuclear factor 4α.Journal of cellular biochemistry · 2019Article
- Induction of Hepatic Metabolic Functions by a Novel Variant of Hepatocyte Nuclear Factor 4γ.Molecular and cellular biology · 2018Article
- Comparison of base-line and chemical-induced transcriptomic responses in HepaRG and RPTEC/TERT1 cells using TempO-Seq.Archives of toxicology · 2018Article
- Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Article
- Effect of dietary saturated fatty acids on HNF-4α DNA binding activity and ApoCIII mRNA in sedentary rat liver.Molecular and cellular biochemistry · 2011Article
- Modulation of hepatocyte nuclear factor-4alpha function by the peroxisome-proliferator-activated receptor-gamma co-activator-1alpha in the acute-phase response.The Biochemical journal · 2008Article
- Nuclear receptor hepatocyte nuclear factor 4alpha1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter.Molecular endocrinology (Baltimore, Md.) · 2008Article
- Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4alpha (HNF4alpha) gene.The Biochemical journal · 2006Article
- Negative autoregulation of HNF-4alpha gene expression by HNF-4alpha1.The Biochemical journal · 2005Article
- Distinct modes of regulation of transcription of hepatitis B virus by the nuclear receptors HNF4alpha and COUP-TF1.Journal of virology · 2003Article
- Hepatocyte nuclear factor 4 response to injury involves a rapid decrease in DNA binding and transactivation via a JAK2 signal transduction pathway.The Biochemical journal · 2002Article
- Hepatocyte nuclear factor (HNF)-4alpha induces expression of endothelial Fas ligand (FasL) to prevent cancer cell transmigration: a novel defense mechanism of endothelium against cancer metastasis.Japanese journal of cancer research : Gann · 2002Article
- Critical roles of nuclear receptor response elements in replication of hepatitis B virus.Journal of virology · 2001Article
- Regulatory mechanisms controlling human hepatocyte nuclear factor 4alpha gene expression.Molecular and cellular biology · 2001Article
- An enhancer element 6 kb upstream of the mouse HNF4alpha1 promoter is activated by glucocorticoids and liver-enriched transcription factors.Nucleic acids research · 2001Article
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The capacity of the liver-enriched transcription factor hepatocyte nuclear factor 4 (HNF4) to direct redifferentiation of dedifferentiated rat hepatoma cells was investigated by stable transfection of epitope-tagged HNF4 cDNA into H5 variant cells. HNF4-producing cells expressed the previously silent HNF1 gene and showed activation of some hepatic functions, including alpha1-antitrypsin, beta-fibrinogen, and transthyretin, but not of the endogenous HNF4 gene. Expression of the other hepatocyte-enriched transcription factors was not modified. Treatment of the HNF4tag-expressing cells with dexamethasone induced expression of the transgene by 10-fold, resulting in enhanced expression of target genes of both glucocorticoid hormones and HNF4. The set of activated hepatic genes was extended by treatment of cells with the demethylating agent 5-azacytidine followed by selection in dexamethasone-containing glucose-free medium. Some of the colonies that developed reexpressed the entire set of hepatic functions tested. Fusion of HNF4tag-producing H5 cells with well-differentiated Fao cells showed that only those hybrids which maintained expression of HNF4tag were protected from complete extinction, including that of the Fao HNF4 gene. Thus, H5 cells must produce an extinguisher of the HNF4 gene. In addition, this result implies that HNF4 itself, or its target HNF1, is a positive regulator of HNF4. In conclusion, HNF4tag expression overcomes repression of the hepatic phenotype of the H5 cell without abolishing its potential to extinguish an active genome. Taken together, these results predict that expression of HNF4 should be sufficient to establish heritable expression of many parameters of the hepatic differentiated state.
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