This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Samadani, U.
Right arrow Articles by Costa, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Samadani, U.
Right arrow Articles by Costa, R. H.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Nov 1996, 6273-6284, Vol 16, No. 11
Copyright © 1996, American Society for Microbiology

The transcriptional activator hepatocyte nuclear factor 6 regulates liver gene expression

U Samadani and RH Costa
Department of Biochemistry, University of Illinois at Chicago, 60612- 7334, USA.

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).


This article has been cited by other articles:

  • Tomaru, Y., Nakanishi, M., Miura, H., Kimura, Y., Ohkawa, H., Ohta, Y., Hayashizaki, Y., Suzuki, M. (2009). Identification of an inter-transcription factor regulatory network in human hepatoma cells by Matrix RNAi. Nucleic Acids Res 37: 1049-1060 [Abstract] [Full Text]  
  • Wederell, E. D., Bilenky, M., Cullum, R., Thiessen, N., Dagpinar, M., Delaney, A., Varhol, R., Zhao, Y., Zeng, T., Bernier, B., Ingham, M., Hirst, M., Robertson, G., Marra, M. A., Jones, S., Hoodless, P. A. (2008). Global analysis of in vivo Foxa2-binding sites in mouse adult liver using massively parallel sequencing. Nucleic Acids Res 36: 4549-4564 [Abstract] [Full Text]  
  • Zhao, H., Friedman, R. D., Fournier, R. E. K. (2007). The Locus Control Region Activates Serpin Gene Expression through Recruitment of Liver-Specific Transcription Factors and RNA Polymerase II. Mol. Cell. Biol. 27: 5286-5295 [Abstract] [Full Text]  
  • Kajiyama, Y., Tian, J., Locker, J. (2006). Characterization of Distant Enhancers and Promoters in the Albumin-{alpha}-Fetoprotein Locus during Active and Silenced Expression. J. Biol. Chem. 281: 30122-30131 [Abstract] [Full Text]  
  • Gillard, G. O., Farr, A. G. (2006). Features of Medullary Thymic Epithelium Implicate Postnatal Development in Maintaining Epithelial Heterogeneity and Tissue-Restricted Antigen Expression. J. Immunol. 176: 5815-5824 [Abstract] [Full Text]  
  • Kim, I.-M., Ramakrishna, S., Gusarova, G. A., Yoder, H. M., Costa, R. H., Kalinichenko, V. V. (2005). The Forkhead Box M1 Transcription Factor Is Essential for Embryonic Development of Pulmonary Vasculature. J. Biol. Chem. 280: 22278-22286 [Abstract] [Full Text]  
  • Baxter, E. W., Cummings, W. J., Fournier, R. E. K. (2005). Formation of a large, complex domain of histone hyperacetylation at human 14q32.1 requires the serpin locus control region. Nucleic Acids Res 33: 3313-3322 [Abstract] [Full Text]  
  • Rausa, F. M. III, Hughes, D. E., Costa, R. H. (2004). Stability of the Hepatocyte Nuclear Factor 6 Transcription Factor Requires Acetylation by the CREB-binding Protein Coactivator. J. Biol. Chem. 279: 43070-43076 [Abstract] [Full Text]  
  • Sheng, W., Yan, H., Rausa, F. M. III, Costa, R. H., Liao, X. (2004). Structure of the Hepatocyte Nuclear Factor 6{alpha} and Its Interaction with DNA. J. Biol. Chem. 279: 33928-33936 [Abstract] [Full Text]  
  • Wiwi, C. A., Gupte, M., Waxman, D. J. (2004). Sexually Dimorphic P450 Gene Expression in Liver-Specific Hepatocyte Nuclear Factor 4{alpha}-Deficient Mice. Mol. Endocrinol. 18: 1975-1987 [Abstract] [Full Text]  
  • Frigeri, C., Martin, C. C., Svitek, C. A., Oeser, J. K., Hutton, J. C., Gannon, M., O'Brien, R. M. (2004). The Proximal Islet-Specific Glucose-6-Phosphatase Catalytic Subunit-Related Protein Autoantigen Promoter Is Sufficient to Initiate but not Maintain Transgene Expression in Mouse Islets in Vivo. Diabetes 53: 1754-1764 [Abstract] [Full Text]  
  • Major, M. L., Lepe, R., Costa, R. H. (2004). Forkhead Box M1B Transcriptional Activity Requires Binding of Cdk-Cyclin Complexes for Phosphorylation-Dependent Recruitment of p300/CBP Coactivators. Mol. Cell. Biol. 24: 2649-2661 [Abstract] [Full Text]  
  • Kalinichenko, V. V., Gusarova, G. A., Kim, I.-M., Shin, B., Yoder, H. M., Clark, J., Sapozhnikov, A. M., Whitsett, J. A., Costa, R. H. (2004). Foxf1 haploinsufficiency reduces Notch-2 signaling during mouse lung development. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L521-L530 [Abstract] [Full Text]  
  • Suzuki, A., Iwama, A., Miyashita, H., Nakauchi, H., Taniguchi, H. (2003). Role for growth factors and extracellular matrix in controlling differentiation of prospectively isolated hepatic stem cells. Development 130: 2513-2524 [Abstract] [Full Text]  
  • Puskas, L. G., Kitajka, K., Nyakas, C., Barcelo-Coblijn, G., Farkas, T. (2003). Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus. Proc. Natl. Acad. Sci. USA 100: 1580-1585 [Abstract] [Full Text]  
  • Rausa, F. M., Tan, Y., Costa, R. H. (2003). Association between Hepatocyte Nuclear Factor 6 (HNF-6) and FoxA2 DNA Binding Domains Stimulates FoxA2 Transcriptional Activity but Inhibits HNF-6 DNA Binding. Mol. Cell. Biol. 23: 437-449 [Abstract] [Full Text]  
  • Schrem, H., Klempnauer, J., Borlak, J. (2002). Liver-Enriched Transcription Factors in Liver Function and Development. Part I: The Hepatocyte Nuclear Factor Network and Liver-Specific Gene Expression. Pharmacol. Rev. 54: 129-158 [Abstract] [Full Text]  
  • Gerrish, K., Cissell, M. A., Stein, R. (2001). The Role of Hepatic Nuclear Factor 1alpha and PDX-1 in Transcriptional Regulation of the pdx-1 Gene. J. Biol. Chem. 276: 47775-47784 [Abstract] [Full Text]  
  • Park, S.-H., Waxman, D. J. (2001). Inhibitory Cross-talk between STAT5b and Liver Nuclear Factor HNF3beta . IMPACT ON THE REGULATION OF GROWTH HORMONE PULSE-STIMULATED, MALE-SPECIFIC LIVER CYTOCHROME P-450 GENE EXPRESSION. J. Biol. Chem. 276: 43031-43039 [Abstract] [Full Text]  
  • White, J. T., Kelly, J. W. (2001). Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influences transthyretin amyloidogenicity invitro. Proc. Natl. Acad. Sci. USA 10.1073/pnas.241406698v1 [Abstract] [Full Text]  
  • Bailly, A., Torres-Padilla, M. E., Tinel, A. P., Weiss, M. C. (2001). An enhancer element 6 kb upstream of the mouse HNF4{alpha}1 promoter is activated by glucocorticoids and liver-enriched transcription factors. Nucleic Acids Res 29: 3495-3505 [Abstract] [Full Text]  
  • Costa, R. H., Kalinichenko, V. V., Lim, L. (2001). Transcription factors in mouse lung development and function. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L823-L838 [Abstract] [Full Text]  
  • Rausa, F. M., Tan, Y., Zhou, H., Yoo, K. W., Stolz, D. B., Watkins, S. C., Franks, R. R., Unterman, T. G., Costa, R. H. (2000). Elevated Levels of Hepatocyte Nuclear Factor 3beta in Mouse Hepatocytes Influence Expression of Genes Involved in Bile Acid and Glucose Homeostasis. Mol. Cell. Biol. 20: 8264-8282 [Abstract] [Full Text]  
  • Choi, H. K., Waxman, D. J. (2000). Plasma Growth Hormone Pulse Activation of Hepatic JAK-STAT5 Signaling: Developmental Regulation and Role in Male-Specific Liver Gene Expression. Endocrinology 141: 3245-3255 [Abstract] [Full Text]  
  • Gerrish, K., Gannon, M., Shih, D., Henderson, E., Stoffel, M., Wright, C. V. E., Stein, R. (2000). Pancreatic beta Cell-specific Transcription of the pdx-1 Gene. THE ROLE OF CONSERVED UPSTREAM CONTROL REGIONS AND THEIR HEPATIC NUCLEAR FACTOR 3beta SITES. J. Biol. Chem. 275: 3485-3492 [Abstract] [Full Text]  
  • Lahuna, O., Rastegar, M., Maiter, D., Thissen, J.-P., Lemaigre, F. P., Rousseau, G. G. (2000). Involvement of STAT5 (Signal Transducer and Activator of Transcription 5) and HNF-4 (Hepatocyte Nuclear Factor 4) in the Transcriptional Control of the hnf6 Gene by Growth Hormone. Mol. Endocrinol. 14: 285-294 [Abstract] [Full Text]  
  • Gannon, M, Ray, M., Van Zee, K, Rausa, F, Costa, R., Wright, C. (2000). Persistent expression of HNF6 in islet endocrine cells causes disrupted islet architecture and loss of beta cell function. Development 127: 2883-2895 [Abstract]  
  • SELDEN, C, KHALIL, M, HODGSON, H J F (1999). What keeps hepatocytes on the straight and narrow? Maintaining differentiated function in the liver. Gut 44: 443-446 [Full Text]  
  • Jacquemin, P., Lannoy, V. J., Rousseau, G. G., Lemaigre, F. P. (1999). OC-2, a Novel Mammalian Member of the ONECUT Class of Homeodomain Transcription Factors Whose Function in Liver Partially Overlaps with That of Hepatocyte Nuclear Factor-6. J. Biol. Chem. 274: 2665-2671 [Abstract] [Full Text]  
  • Diarra-Mehrpour, M., Sarafan, N., Bourguignon, J., Bonnet, F., Bost, F., Martin, J.-P. (1998). Human Inter-alpha -Trypsin Inhibitor Heavy Chain H3 Gene. GENOMIC ORGANIZATION, PROMOTER ANALYSIS, AND GENE LINKAGE. J. Biol. Chem. 273: 26809-26819 [Abstract] [Full Text]  
  • Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., Chatterjee, B. (1998). Tissue-specific and Androgen-repressible Regulation of the Rat Dehydroepiandrosterone Sulfotransferase Gene Promoter. J. Biol. Chem. 273: 21856-21866 [Abstract] [Full Text]  
  • Jetton, T. L., Moates, J. M., Lindner, J., Wright, C. V. E., Magnuson, M. A. (1998). Targeted oncogenesis of hormone-negative pancreatic islet progenitor cells. Proc. Natl. Acad. Sci. USA 95: 8654-8659 [Abstract] [Full Text]  
  • Lannoy, V. J., Burglin, T. R., Rousseau, G. G., Lemaigre, F. P. (1998). Isoforms of Hepatocyte Nuclear Factor-6 Differ in DNA-binding Properties, Contain a Bifunctional Homeodomain, and Define the New ONECUT Class of Homeodomain Proteins. J. Biol. Chem. 273: 13552-13562 [Abstract] [Full Text]  
  • Spek, C. A., Lannoy, V. J., Lemaigre, F. P., Rousseau, G. G., Bertina, R. M., Reitsma, P. H. (1998). Type I Protein C Deficiency Caused by Disruption of a Hepatocyte Nuclear Factor (HNF)-6/HNF-1 Binding Site in the Human Protein C Gene Promoter. J. Biol. Chem. 273: 10168-10173 [Abstract] [Full Text]  
  • Lahuna, O., Fernandez, L., Karlsson, H., Maiter, D., Lemaigre, F. P., Rousseau, G. G., Gustafsson, J.-A., Mode, A. (1997). Expression of hepatocyte nuclear factor 6 in rat liver is sex-dependent and regulated by growth hormone. Proc. Natl. Acad. Sci. USA 94: 12309-12313 [Abstract] [Full Text]  
  • Yao, K.-M., Sha, M., Lu, Z., Wong, G. G. (1997). Molecular Analysis of a Novel Winged Helix Protein, WIN. EXPRESSION PATTERN, DNA BINDING PROPERTY, AND ALTERNATIVE SPLICING WITHIN THE DNA BINDING DOMAIN. J. Biol. Chem. 272: 19827-19836 [Abstract] [Full Text]  
  • Lim, L., Zhou, H., Costa, R. H. (1997). The winged helix transcription factor HFH-4 is expressed during choroid plexus epithelial development in the mouse embryo. Proc. Natl. Acad. Sci. USA 94: 3094-3099 [Abstract] [Full Text]  
  • Lannoy, V. J., Rodolosse, A., Pierreux, C. E., Rousseau, G. G., Lemaigre, F. P. (2000). Transcriptional Stimulation by Hepatocyte Nuclear Factor-6. TARGET-SPECIFIC RECRUITMENT OF EITHER CREB-BINDING PROTEIN (CBP) or p300/CBP-ASSOCIATED FACTOR (p/CAF). J. Biol. Chem. 275: 22098-22103 [Abstract] [Full Text]  
  • Delesque-Touchard, N., Park, S.-H., Waxman, D. J. (2000). Synergistic Action of Hepatocyte Nuclear Factors 3 and 6 on CYP2C12 Gene Expression and Suppression by Growth Hormone-activated STAT5b. PROPOSED MODEL FOR FEMALE-SPECIFIC EXPRESSION OF CYP2C12 IN ADULT RAT LIVER. J. Biol. Chem. 275: 34173-34182 [Abstract] [Full Text]  
  • Pare, J.-F., Roy, S., Galarneau, L., Belanger, L. (2001). The Mouse Fetoprotein Transcription Factor (FTF) Gene Promoter Is Regulated by Three GATA Elements with Tandem E Box and Nkx Motifs, and FTF in Turn Activates the Hnf3beta , Hnf4alpha , and Hnf1alpha Gene Promoters. J. Biol. Chem. 276: 13136-13144 [Abstract] [Full Text]  
  • Streeper, R. S., Hornbuckle, L. A., Svitek, C. A., Goldman, J. K., Oeser, J. K., O'Brien, R. M. (2001). Protein Kinase A Phosphorylates Hepatocyte Nuclear Factor-6 and Stimulates Glucose-6-phosphatase Catalytic Subunit Gene Transcription. J. Biol. Chem. 276: 19111-19118 [Abstract] [Full Text]  
  • Godbout, R., Monckton, E. A. (2001). Differential Regulation of the Aldehyde Dehydrogenase 1 Gene in Embryonic Chick Retina and Liver. J. Biol. Chem. 276: 32896-32904 [Abstract] [Full Text]  
  • White, J. T., Kelly, J. W. (2001). Support for the multigenic hypothesis of amyloidosis: The binding stoichiometry of retinol-binding protein, vitamin A, and thyroid hormone influences transthyretin amyloidogenicity invitro. Proc. Natl. Acad. Sci. USA 98: 13019-13024 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»