Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1996 Nov;16(11):6273–6284. doi: 10.1128/mcb.16.11.6273

The transcriptional activator hepatocyte nuclear factor 6 regulates liver gene expression.

U Samadani 1, R H Costa 1
PMCID: PMC231630  PMID: 8887657

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).

Full Text

The Full Text of this article is available as a PDF (2.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ang S. L., Rossant J. HNF-3 beta is essential for node and notochord formation in mouse development. Cell. 1994 Aug 26;78(4):561–574. doi: 10.1016/0092-8674(94)90522-3. [DOI] [PubMed] [Google Scholar]
  3. Ang S. L., Wierda A., Wong D., Stevens K. A., Cascio S., Rossant J., Zaret K. S. The formation and maintenance of the definitive endoderm lineage in the mouse: involvement of HNF3/forkhead proteins. Development. 1993 Dec;119(4):1301–1315. doi: 10.1242/dev.119.4.1301. [DOI] [PubMed] [Google Scholar]
  4. Augé-Gouillou C., Petropoulos I., Zakin M. M. Liver-enriched HNF-3 alpha and ubiquitous factors interact with the human transferrin gene enhancer. FEBS Lett. 1993 May 24;323(1-2):4–10. doi: 10.1016/0014-5793(93)81436-4. [DOI] [PubMed] [Google Scholar]
  5. Baumhueter S., Mendel D. B., Conley P. B., Kuo C. J., Turk C., Graves M. K., Edwards C. A., Courtois G., Crabtree G. R. HNF-1 shares three sequence motifs with the POU domain proteins and is identical to LF-B1 and APF. Genes Dev. 1990 Mar;4(3):372–379. doi: 10.1101/gad.4.3.372. [DOI] [PubMed] [Google Scholar]
  6. Bergad P. L., Shih H. M., Towle H. C., Schwarzenberg S. J., Berry S. A. Growth hormone induction of hepatic serine protease inhibitor 2.1 transcription is mediated by a Stat5-related factor binding synergistically to two gamma-activated sites. J Biol Chem. 1995 Oct 20;270(42):24903–24910. doi: 10.1074/jbc.270.42.24903. [DOI] [PubMed] [Google Scholar]
  7. Brooks A. R., Blackhart B. D., Haubold K., Levy-Wilson B. Characterization of tissue-specific enhancer elements in the second intron of the human apolipoprotein B gene. J Biol Chem. 1991 Apr 25;266(12):7848–7859. [PubMed] [Google Scholar]
  8. Cao Z., Umek R. M., McKnight S. L. Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991 Sep;5(9):1538–1552. doi: 10.1101/gad.5.9.1538. [DOI] [PubMed] [Google Scholar]
  9. Chen M., Hieng S., Qian X., Costa R., Ou J. H. Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3. Virology. 1994 Nov 15;205(1):127–132. doi: 10.1006/viro.1994.1627. [DOI] [PubMed] [Google Scholar]
  10. Clark K. L., Halay E. D., Lai E., Burley S. K. Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature. 1993 Jul 29;364(6436):412–420. doi: 10.1038/364412a0. [DOI] [PubMed] [Google Scholar]
  11. Costa R. H., Grayson D. R., Darnell J. E., Jr Multiple hepatocyte-enriched nuclear factors function in the regulation of transthyretin and alpha 1-antitrypsin genes. Mol Cell Biol. 1989 Apr;9(4):1415–1425. doi: 10.1128/mcb.9.4.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Costa R. H., Grayson D. R. Site-directed mutagenesis of hepatocyte nuclear factor (HNF) binding sites in the mouse transthyretin (TTR) promoter reveal synergistic interactions with its enhancer region. Nucleic Acids Res. 1991 Aug 11;19(15):4139–4145. doi: 10.1093/nar/19.15.4139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Costa R. H., Grayson D. R., Xanthopoulos K. G., Darnell J. E., Jr A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3840–3844. doi: 10.1073/pnas.85.11.3840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Costa R. H., Van Dyke T. A., Yan C., Kuo F., Darnell J. E., Jr Similarities in transthyretin gene expression and differences in transcription factors: liver and yolk sac compared to choroid plexus. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6589–6593. doi: 10.1073/pnas.87.17.6589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  16. Descombes P., Chojkier M., Lichtsteiner S., Falvey E., Schibler U. LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes Dev. 1990 Sep;4(9):1541–1551. doi: 10.1101/gad.4.9.1541. [DOI] [PubMed] [Google Scholar]
  17. DiPersio C. M., Jackson D. A., Zaret K. S. The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology. Mol Cell Biol. 1991 Sep;11(9):4405–4414. doi: 10.1128/mcb.11.9.4405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Drolet D. W., Scully K. M., Simmons D. M., Wegner M., Chu K. T., Swanson L. W., Rosenfeld M. G. TEF, a transcription factor expressed specifically in the anterior pituitary during embryogenesis, defines a new class of leucine zipper proteins. Genes Dev. 1991 Oct;5(10):1739–1753. doi: 10.1101/gad.5.10.1739. [DOI] [PubMed] [Google Scholar]
  19. Frain M., Swart G., Monaci P., Nicosia A., Stämpfli S., Frank R., Cortese R. The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain. Cell. 1989 Oct 6;59(1):145–157. doi: 10.1016/0092-8674(89)90877-5. [DOI] [PubMed] [Google Scholar]
  20. Fung W. P., Thomas T., Dickson P. W., Aldred A. R., Milland J., Dziadek M., Power B., Hudson P., Schreiber G. Structure and expression of the rat transthyretin (prealbumin) gene. J Biol Chem. 1988 Jan 5;263(1):480–488. [PubMed] [Google Scholar]
  21. Groupp E. R., Crawford N., Locker J. Characterization of the distal alpha-fetoprotein enhancer, a strong, long distance, liver-specific activator. J Biol Chem. 1994 Sep 2;269(35):22178–22187. [PubMed] [Google Scholar]
  22. Harnish D. C., Malik S., Karathanasis S. K. Activation of apolipoprotein AI gene transcription by the liver-enriched factor HNF-3. J Biol Chem. 1994 Nov 11;269(45):28220–28226. [PubMed] [Google Scholar]
  23. Ho S. N., Hunt H. D., Horton R. M., Pullen J. K., Pease L. R. Site-directed mutagenesis by overlap extension using the polymerase chain reaction. Gene. 1989 Apr 15;77(1):51–59. doi: 10.1016/0378-1119(89)90358-2. [DOI] [PubMed] [Google Scholar]
  24. Hromas R., Costa R. The hepatocyte nuclear factor-3/forkhead transcription regulatory family in development, inflammation, and neoplasia. Crit Rev Oncol Hematol. 1995 Aug;20(1-2):129–140. doi: 10.1016/1040-8428(94)00151-i. [DOI] [PubMed] [Google Scholar]
  25. Hunger S. P., Ohyashiki K., Toyama K., Cleary M. L. Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. Genes Dev. 1992 Sep;6(9):1608–1620. doi: 10.1101/gad.6.9.1608. [DOI] [PubMed] [Google Scholar]
  26. Ikeda K., Shaw-White J. R., Wert S. E., Whitsett J. A. Hepatocyte nuclear factor 3 activates transcription of thyroid transcription factor 1 in respiratory epithelial cells. Mol Cell Biol. 1996 Jul;16(7):3626–3636. doi: 10.1128/mcb.16.7.3626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Inaba T., Roberts W. M., Shapiro L. H., Jolly K. W., Raimondi S. C., Smith S. D., Look A. T. Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science. 1992 Jul 24;257(5069):531–534. doi: 10.1126/science.1386162. [DOI] [PubMed] [Google Scholar]
  28. Ip Y. T., Poon D., Stone D., Granner D. K., Chalkley R. Interaction of a liver-specific factor with an enhancer 4.8 kilobases upstream of the phosphoenolpyruvate carboxykinase gene. Mol Cell Biol. 1990 Jul;10(7):3770–3781. doi: 10.1128/mcb.10.7.3770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Iyer S. V., Davis D. L., Seal S. N., Burch J. B. Chicken vitellogenin gene-binding protein, a leucine zipper transcription factor that binds to an important control element in the chicken vitellogenin II promoter, is related to rat DBP. Mol Cell Biol. 1991 Oct;11(10):4863–4875. doi: 10.1128/mcb.11.10.4863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jacob A., Budhiraja S., Qian X., Clevidence D., Costa R. H., Reichel R. R. Retinoic acid-mediated activation of HNF-3 alpha during EC stem cell differentiation. Nucleic Acids Res. 1994 Jun 11;22(11):2126–2133. doi: 10.1093/nar/22.11.2126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. James R., Erler T., Kazenwadel J. Structure of the murine homeobox gene cdx-2. Expression in embryonic and adult intestinal epithelium. J Biol Chem. 1994 May 27;269(21):15229–15237. [PubMed] [Google Scholar]
  32. Johnson D., Harrison S., Pineda N., Heinlein C., al-Shawi R., Bishop J. O. Localization of the response elements of a gene induced by intermittent growth hormone stimulation. J Mol Endocrinol. 1995 Feb;14(1):35–49. doi: 10.1677/jme.0.0140035. [DOI] [PubMed] [Google Scholar]
  33. Kaestner K. H., Hiemisch H., Luckow B., Schütz G. The HNF-3 gene family of transcription factors in mice: gene structure, cDNA sequence, and mRNA distribution. Genomics. 1994 Apr;20(3):377–385. doi: 10.1006/geno.1994.1191. [DOI] [PubMed] [Google Scholar]
  34. Kinoshita S., Akira S., Kishimoto T. A member of the C/EBP family, NF-IL6 beta, forms a heterodimer and transcriptionally synergizes with NF-IL6. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1473–1476. doi: 10.1073/pnas.89.4.1473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kuo C. J., Conley P. B., Chen L., Sladek F. M., Darnell J. E., Jr, Crabtree G. R. A transcriptional hierarchy involved in mammalian cell-type specification. Nature. 1992 Jan 30;355(6359):457–461. doi: 10.1038/355457a0. [DOI] [PubMed] [Google Scholar]
  36. Ladias J. A., Karathanasis S. K. Regulation of the apolipoprotein AI gene by ARP-1, a novel member of the steroid receptor superfamily. Science. 1991 Feb 1;251(4993):561–565. doi: 10.1126/science.1899293. [DOI] [PubMed] [Google Scholar]
  37. Lai E., Prezioso V. R., Smith E., Litvin O., Costa R. H., Darnell J. E., Jr HNF-3A, a hepatocyte-enriched transcription factor of novel structure is regulated transcriptionally. Genes Dev. 1990 Aug;4(8):1427–1436. doi: 10.1101/gad.4.8.1427. [DOI] [PubMed] [Google Scholar]
  38. Lai E., Prezioso V. R., Tao W. F., Chen W. S., Darnell J. E., Jr Hepatocyte nuclear factor 3 alpha belongs to a gene family in mammals that is homologous to the Drosophila homeotic gene fork head. Genes Dev. 1991 Mar;5(3):416–427. doi: 10.1101/gad.5.3.416. [DOI] [PubMed] [Google Scholar]
  39. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  40. Landschulz W. H., Johnson P. F., McKnight S. L. The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. Science. 1989 Mar 31;243(4899):1681–1688. doi: 10.1126/science.2494700. [DOI] [PubMed] [Google Scholar]
  41. Laverriere A. C., MacNeill C., Mueller C., Poelmann R. E., Burch J. B., Evans T. GATA-4/5/6, a subfamily of three transcription factors transcribed in developing heart and gut. J Biol Chem. 1994 Sep 16;269(37):23177–23184. [PubMed] [Google Scholar]
  42. Legraverend C., Eguchi H., Ström A., Lahuna O., Mode A., Tollet P., Westin S., Gustafsson J. A. Transactivation of the rat CYP2C13 gene promoter involves HNF-1, HNF-3, and members of the orphan receptor subfamily. Biochemistry. 1994 Aug 23;33(33):9889–9897. doi: 10.1021/bi00199a010. [DOI] [PubMed] [Google Scholar]
  43. Lemaigre F. P., Durviaux S. M., Rousseau G. G. Liver-specific factor binding to the liver promoter of a 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene. J Biol Chem. 1993 Sep 15;268(26):19896–19905. [PubMed] [Google Scholar]
  44. Liu J. K., DiPersio C. M., Zaret K. S. Extracellular signals that regulate liver transcription factors during hepatic differentiation in vitro. Mol Cell Biol. 1991 Feb;11(2):773–784. doi: 10.1128/mcb.11.2.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. McPherson C. E., Shim E. Y., Friedman D. S., Zaret K. S. An active tissue-specific enhancer and bound transcription factors existing in a precisely positioned nucleosomal array. Cell. 1993 Oct 22;75(2):387–398. doi: 10.1016/0092-8674(93)80079-t. [DOI] [PubMed] [Google Scholar]
  46. Molowa D. T., Chen W. S., Cimis G. M., Tan C. P. Transcriptional regulation of the human cholesterol 7 alpha-hydroxylase gene. Biochemistry. 1992 Mar 10;31(9):2539–2544. doi: 10.1021/bi00124a014. [DOI] [PubMed] [Google Scholar]
  47. Monaghan A. P., Kaestner K. H., Grau E., Schütz G. Postimplantation expression patterns indicate a role for the mouse forkhead/HNF-3 alpha, beta and gamma genes in determination of the definitive endoderm, chordamesoderm and neuroectoderm. Development. 1993 Nov;119(3):567–578. doi: 10.1242/dev.119.3.567. [DOI] [PubMed] [Google Scholar]
  48. Mueller C. R., Maire P., Schibler U. DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell. 1990 Apr 20;61(2):279–291. doi: 10.1016/0092-8674(90)90808-r. [DOI] [PubMed] [Google Scholar]
  49. Nagy P., Bisgaard H. C., Thorgeirsson S. S. Expression of hepatic transcription factors during liver development and oval cell differentiation. J Cell Biol. 1994 Jul;126(1):223–233. doi: 10.1083/jcb.126.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Nitsch D., Boshart M., Schütz G. Activation of the tyrosine aminotransferase gene is dependent on synergy between liver-specific and hormone-responsive elements. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5479–5483. doi: 10.1073/pnas.90.12.5479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Ori A., Shaul Y. Hepatitis B virus enhancer binds and is activated by the Hepatocyte nuclear factor 3. Virology. 1995 Feb 20;207(1):98–106. doi: 10.1006/viro.1995.1055. [DOI] [PubMed] [Google Scholar]
  52. Overdier D. G., Porcella A., Costa R. H. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol. 1994 Apr;14(4):2755–2766. doi: 10.1128/mcb.14.4.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Pani L., Quian X. B., Clevidence D., Costa R. H. The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation. Mol Cell Biol. 1992 Feb;12(2):552–562. doi: 10.1128/mcb.12.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Pellerin I., Schnabel C., Catron K. M., Abate C. Hox proteins have different affinities for a consensus DNA site that correlate with the positions of their genes on the hox cluster. Mol Cell Biol. 1994 Jul;14(7):4532–4545. doi: 10.1128/mcb.14.7.4532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Poli V., Mancini F. P., Cortese R. IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990 Nov 2;63(3):643–653. doi: 10.1016/0092-8674(90)90459-r. [DOI] [PubMed] [Google Scholar]
  56. Qian X., Costa R. H. Analysis of hepatocyte nuclear factor-3 beta protein domains required for transcriptional activation and nuclear targeting. Nucleic Acids Res. 1995 Apr 11;23(7):1184–1191. doi: 10.1093/nar/23.7.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Qian X., Samadani U., Porcella A., Costa R. H. Decreased expression of hepatocyte nuclear factor 3 alpha during the acute-phase response influences transthyretin gene transcription. Mol Cell Biol. 1995 Mar;15(3):1364–1376. doi: 10.1128/mcb.15.3.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Raney A. K., Zhang P., McLachlan A. Regulation of transcription from the hepatitis B virus large surface antigen promoter by hepatocyte nuclear factor 3. J Virol. 1995 Jun;69(6):3265–3272. doi: 10.1128/jvi.69.6.3265-3272.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Raymondjean M., Pichard A. L., Gregori C., Ginot F., Kahn A. Interplay of an original combination of factors: C/EBP, NFY, HNF3, and HNF1 in the rat aldolase B gene promoter. Nucleic Acids Res. 1991 Nov 25;19(22):6145–6153. doi: 10.1093/nar/19.22.6145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Reichel R. R., Budhiraja S., Jacob A. Delayed activation of HNF-3 beta upon retinoic acid-induced teratocarcinoma cell differentiation. Exp Cell Res. 1994 Oct;214(2):634–641. doi: 10.1006/excr.1994.1301. [DOI] [PubMed] [Google Scholar]
  61. Rigaud G., Roux J., Pictet R., Grange T. In vivo footprinting of rat TAT gene: dynamic interplay between the glucocorticoid receptor and a liver-specific factor. Cell. 1991 Nov 29;67(5):977–986. doi: 10.1016/0092-8674(91)90370-e. [DOI] [PubMed] [Google Scholar]
  62. Roux J., Pictet R., Grange T. Hepatocyte nuclear factor 3 determines the amplitude of the glucocorticoid response of the rat tyrosine aminotransferase gene. DNA Cell Biol. 1995 May;14(5):385–396. doi: 10.1089/dna.1995.14.385. [DOI] [PubMed] [Google Scholar]
  63. Ruiz i Altaba A., Prezioso V. R., Darnell J. E., Jessell T. M. Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate. Mech Dev. 1993 Dec;44(2-3):91–108. doi: 10.1016/0925-4773(93)90060-b. [DOI] [PubMed] [Google Scholar]
  64. Samadani U., Porcella A., Pani L., Johnson P. F., Burch J. B., Pine R., Costa R. H. Cytokine regulation of the liver transcription factor hepatocyte nuclear factor-3 beta is mediated by the C/EBP family and interferon regulatory factor 1. Cell Growth Differ. 1995 Jul;6(7):879–890. [PubMed] [Google Scholar]
  65. Samadani U., Qian X., Costa R. H. Identification of a transthyretin enhancer site that selectively binds the hepatocyte nuclear factor-3 beta isoform. Gene Expr. 1996;6(1):23–33. [PMC free article] [PubMed] [Google Scholar]
  66. Sasaki H., Hogan B. L. Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development. 1993 May;118(1):47–59. doi: 10.1242/dev.118.1.47. [DOI] [PubMed] [Google Scholar]
  67. Sasaki H., Hogan B. L. HNF-3 beta as a regulator of floor plate development. Cell. 1994 Jan 14;76(1):103–115. doi: 10.1016/0092-8674(94)90176-7. [DOI] [PubMed] [Google Scholar]
  68. Sawaya P. L., Stripp B. R., Whitsett J. A., Luse D. S. The lung-specific CC10 gene is regulated by transcription factors from the AP-1, octamer, and hepatocyte nuclear factor 3 families. Mol Cell Biol. 1993 Jul;13(7):3860–3871. doi: 10.1128/mcb.13.7.3860. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Shaw P. M., Weiss M. C., Adesnik M. Hepatocyte nuclear factor 3 is a major determinant of CYP2C6 promoter activity in hepatoma cells. Mol Pharmacol. 1994 Jul;46(1):79–87. [PubMed] [Google Scholar]
  70. Simon T. C., Roth K. A., Gordon J. I. Use of transgenic mice to map cis-acting elements in the liver fatty acid-binding protein gene (Fabpl) that regulate its cell lineage-specific, differentiation-dependent, and spatial patterns of expression in the gut epithelium and in the liver acinus. J Biol Chem. 1993 Aug 25;268(24):18345–18358. [PubMed] [Google Scholar]
  71. Sladek F. M., Zhong W. M., Lai E., Darnell J. E., Jr Liver-enriched transcription factor HNF-4 is a novel member of the steroid hormone receptor superfamily. Genes Dev. 1990 Dec;4(12B):2353–2365. doi: 10.1101/gad.4.12b.2353. [DOI] [PubMed] [Google Scholar]
  72. Spek C. A., Greengard J. S., Griffin J. H., Bertina R. M., Reitsma P. H. Two mutations in the promoter region of the human protein C gene both cause type I protein C deficiency by disruption of two HNF-3 binding sites. J Biol Chem. 1995 Oct 13;270(41):24216–24221. doi: 10.1074/jbc.270.41.24216. [DOI] [PubMed] [Google Scholar]
  73. Suh E., Chen L., Taylor J., Traber P. G. A homeodomain protein related to caudal regulates intestine-specific gene transcription. Mol Cell Biol. 1994 Nov;14(11):7340–7351. doi: 10.1128/mcb.14.11.7340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Suh E., Traber P. G. An intestine-specific homeobox gene regulates proliferation and differentiation. Mol Cell Biol. 1996 Feb;16(2):619–625. doi: 10.1128/mcb.16.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Traber P. G., Wu G. D., Wang W. Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene. Mol Cell Biol. 1992 Aug;12(8):3614–3627. doi: 10.1128/mcb.12.8.3614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Unterman T. G., Fareeduddin A., Harris M. A., Goswami R. G., Porcella A., Costa R. H., Lacson R. G. Hepatocyte nuclear factor-3 (HNF-3) binds to the insulin response sequence in the IGF binding protein-1 (IGFBP-1) promoter and enhances promoter function. Biochem Biophys Res Commun. 1994 Sep 30;203(3):1835–1841. doi: 10.1006/bbrc.1994.2401. [DOI] [PubMed] [Google Scholar]
  77. Vallet V., Antoine B., Chafey P., Vandewalle A., Kahn A. Overproduction of a truncated hepatocyte nuclear factor 3 protein inhibits expression of liver-specific genes in hepatoma cells. Mol Cell Biol. 1995 Oct;15(10):5453–5460. doi: 10.1128/mcb.15.10.5453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Weigel D., Jäckle H. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990 Nov 2;63(3):455–456. doi: 10.1016/0092-8674(90)90439-l. [DOI] [PubMed] [Google Scholar]
  79. Weinstein D. C., Ruiz i Altaba A., Chen W. S., Hoodless P., Prezioso V. R., Jessell T. M., Darnell J. E., Jr The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. Cell. 1994 Aug 26;78(4):575–588. doi: 10.1016/0092-8674(94)90523-1. [DOI] [PubMed] [Google Scholar]
  80. Williams S. C., Cantwell C. A., Johnson P. F. A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Genes Dev. 1991 Sep;5(9):1553–1567. doi: 10.1101/gad.5.9.1553. [DOI] [PubMed] [Google Scholar]
  81. Yan C., Costa R. H., Darnell J. E., Jr, Chen J. D., Van Dyke T. A. Distinct positive and negative elements control the limited hepatocyte and choroid plexus expression of transthyretin in transgenic mice. EMBO J. 1990 Mar;9(3):869–878. doi: 10.1002/j.1460-2075.1990.tb08184.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Zhong W., Mirkovitch J., Darnell J. E., Jr Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression. Mol Cell Biol. 1994 Nov;14(11):7276–7284. doi: 10.1128/mcb.14.11.7276. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES