ArticleMolecular and cellular biology1996
The transcriptional activator hepatocyte nuclear factor 6 regulates liver gene expression.
Article in Molecular and cellular biology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Loss of HNF6 expression correlates with human pancreatic cancer progression.Laboratory investigation; a journal of technical methods and pathology · 2014Pooled it
- Review
- Role of HNF6 in liver homeostasis and pathophysiology.Molecular medicine (Cambridge, Mass.) · 2025Review
- CUT homeobox genes: transcriptional regulation of neuronal specification and beyond.Frontiers in cellular neuroscience · 2023Review
- Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells.Gastroenterology · 2018Review
- Cooperative function of Pdx1 and Oc1 in multipotent pancreatic progenitors impacts postnatal islet maturation and adaptability.American journal of physiology. Endocrinology and metabolism · 2018Article
- Loss of liver-specific and sexually dimorphic gene expression by aryl hydrocarbon receptor activation in C57BL/6 mice.PloS one · 2017Article
- HNF6 and Rev-erbα integrate hepatic lipid metabolism by overlapping and distinct transcriptional mechanisms.Genes & development · 2016Article
- Hepatitis B Virus X Protein Induces Hepatic Steatosis by Enhancing the Expression of Liver Fatty Acid Binding Protein.Journal of virology · 2016Article
- Krüppel-like Factor 4 Blocks Hepatocellular Carcinoma Dedifferentiation and Progression through Activation of Hepatocyte Nuclear Factor-6.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Onecut transcription factors in development and disease.Trends in developmental biology · 2016Article
- Bioinformatic screening of autoimmune disease genes and protein structure prediction with FAMS for drug discovery.Protein and peptide letters · 2014Article
- Age-related and depot-specific changes in white adipose tissue of growth hormone receptor-null mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2014Article
- Hepatocyte nuclear factor 6 suppresses the migration and invasive growth of lung cancer cells through p53 and the inhibition of epithelial-mesenchymal transition.The Journal of biological chemistry · 2013Article
- Onecut1 is essential for horizontal cell genesis and retinal integrity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Otx2 and Onecut1 promote the fates of cone photoreceptors and horizontal cells and repress rod photoreceptors.Developmental cell · 2013Article
- Evaluation of tafamidis as first-line therapeutic agent for transthyretin familial amyloidotic polyneuropathy.Degenerative neurological and neuromuscular disease · 2012Review
- Hepatocyte nuclear factor-4α interacts with other hepatocyte nuclear factors in regulating transthyretin gene expression.The FEBS journal · 2010Article
- Differential transcriptional characteristics of small and large biliary epithelial cells derived from small and large bile ducts.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Tissue-specific activation of mitogen-activated protein kinases for expression of transthyretin by phenylalanine and its metabolite, phenylpyruvic acid.Experimental & molecular medicine · 2010Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The hepatocyte nuclear factor 3(alpha) (HNF-3(alpha)), -3(beta), and -3(gamma) proteins share homology in the winged-helix/fork head DNA binding domain and mediate hepatocyte-enriched transcription of numerous genes whose expression is necessary for organ function. In this work, we identify a liver-enriched transcription factor, HNF-6, which recognizes the -138 to -126 region of the HNF-3(beta) promoter and binds the original HNF-3 site of the transthyretin promoter (-94 to -106). We show that HNF-6 and HNF-3 possess different DNA binding specificities by competition and methylation interference studies and are immunologically distinct. Site-directed mutagenesis of the HNF-6 sites in the HNF-3(beta) and transthyretin promoters diminishes reporter gene expression, suggesting that HNF-6 activates transcription of these promoters. Using the HNF-6 binding sequence DHWATTGAYTWWD (where W = A or T, Y = T or C, H is not G, and D is not C) determined by sequence comparison and methylation interference, we predicted that HNF-6 will bind to 22 additional hepatocyte-enriched genes. Of these potential target genes, we selected seven of the HNF-6 binding sequences and demonstrated that they bind the HNF-6 protein. These include promoter sequences from alpha-2 urinary globulin, alpha-1 antitrypsin, cytochrome P-450 2C13, L-type 6-phosphofructo-2-kinase, mouse major urinary protein, tryptophan oxygenase, and alpha-fetoprotein genes. HNF-6 binding activity was also found in the intestinal epithelial cell line HT29, and potential HNF-6 binding sites were present in intestinal sucrase isomaltase, cdx-2 homeodomain protein, and intestinal fatty acid binding protein promoter regions. These studies suggest that HNF-6 may regulate hepatocyte-specific genes and may play a role in epithelial cell differentiation of gut endoderm via regulation of HNF-3(beta).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.