Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1993 Aug 11;21(16):3731–3736. doi: 10.1093/nar/21.16.3731

Analysis of the rat hepatocyte nuclear factor (HNF) 1 gene promoter: synergistic activation by HNF4 and HNF1 proteins.

N Miura 1, K Tanaka 1
PMCID: PMC309877  PMID: 8367288

Abstract

Hepatocyte nuclear factor (HNF) 1 is a key transcription factor involved in the expression of many liver-specific genes. We have isolated and characterized the promoter region of the rat HNF1 gene. Transfection experiments revealed that a short region between -118 and -8 is crucial for cell type-specific expression of the HNF1 gene in the hepatoma cell line, HepG2 cells. This region contains two positive cis-elements: site A, to which the transcription factor HNF4 protein can bind, and site B, to which the HNF1 protein can bind. Mutational analyses of these sites and cotransfection assays suggested that the HNF4 protein and HNF1 protein can transactivate the HNF1 gene.

Full text

PDF
3731

Images in this article

Selected References

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

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen R. P., Ingraham H. A., Treacy M. N., Albert V. R., Wilson L., Rosenfeld M. G. Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements. Nature. 1990 Aug 9;346(6284):583–586. doi: 10.1038/346583a0. [DOI] [PubMed] [Google Scholar]
  4. Courtois G., Morgan J. G., Campbell L. A., Fourel G., Crabtree G. R. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987 Oct 30;238(4827):688–692. doi: 10.1126/science.3499668. [DOI] [PubMed] [Google Scholar]
  5. De Simone V., De Magistris L., Lazzaro D., Gerstner J., Monaci P., Nicosia A., Cortese R. LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia. EMBO J. 1991 Jun;10(6):1435–1443. doi: 10.1002/j.1460-2075.1991.tb07664.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorski K., Carneiro M., Schibler U. Tissue-specific in vitro transcription from the mouse albumin promoter. Cell. 1986 Dec 5;47(5):767–776. doi: 10.1016/0092-8674(86)90519-2. [DOI] [PubMed] [Google Scholar]
  9. Hata S., Tsukamoto T., Osumi T. A novel isoform of rat hepatocyte nuclear factor 4 (HNF-4). Biochim Biophys Acta. 1992 Jun 15;1131(2):211–213. doi: 10.1016/0167-4781(92)90080-j. [DOI] [PubMed] [Google Scholar]
  10. Ingham P. W. The molecular genetics of embryonic pattern formation in Drosophila. Nature. 1988 Sep 1;335(6185):25–34. doi: 10.1038/335025a0. [DOI] [PubMed] [Google Scholar]
  11. Kemler I., Schaffner W. Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression. FASEB J. 1990 Mar;4(5):1444–1449. doi: 10.1096/fasebj.4.5.2407588. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kuo C. J., Mendel D. B., Hansen L. P., Crabtree G. R. Independent regulation of HNF-1 alpha and HNF-1 beta by retinoic acid in F9 teratocarcinoma cells. EMBO J. 1991 Aug;10(8):2231–2236. doi: 10.1002/j.1460-2075.1991.tb07759.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  18. McCormick A., Brady H., Theill L. E., Karin M. Regulation of the pituitary-specific homeobox gene GHF1 by cell-autonomous and environmental cues. Nature. 1990 Jun 28;345(6278):829–832. doi: 10.1038/345829a0. [DOI] [PubMed] [Google Scholar]
  19. Mendel D. B., Crabtree G. R. HNF-1, a member of a novel class of dimerizing homeodomain proteins. J Biol Chem. 1991 Jan 15;266(2):677–680. [PubMed] [Google Scholar]
  20. Mendel D. B., Hansen L. P., Graves M. K., Conley P. B., Crabtree G. R. HNF-1 alpha and HNF-1 beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro. Genes Dev. 1991 Jun;5(6):1042–1056. doi: 10.1101/gad.5.6.1042. [DOI] [PubMed] [Google Scholar]
  21. Miura N., Iwai K., Miyamoto I. Immunological characterization of hepatocyte nuclear factor 1 protein: appearance of hepatocyte nuclear factor 1 protein in developing mouse embryos. Eur J Cell Biol. 1993 Apr;60(2):376–382. [PubMed] [Google Scholar]
  22. Mizushima S., Nagata S. pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 1990 Sep 11;18(17):5322–5322. doi: 10.1093/nar/18.17.5322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Niwa H., Yamamura K., Miyazaki J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991 Dec 15;108(2):193–199. doi: 10.1016/0378-1119(91)90434-d. [DOI] [PubMed] [Google Scholar]
  24. Olson E. N. MyoD family: a paradigm for development? Genes Dev. 1990 Sep;4(9):1454–1461. doi: 10.1101/gad.4.9.1454. [DOI] [PubMed] [Google Scholar]
  25. Ott M. O., Rey-Campos J., Cereghini S., Yaniv M. vHNF1 is expressed in epithelial cells of distinct embryonic origin during development and precedes HNF1 expression. Mech Dev. 1991 Dec;36(1-2):47–58. doi: 10.1016/0925-4773(91)90071-d. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Rey-Campos J., Chouard T., Yaniv M., Cereghini S. vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1. EMBO J. 1991 Jun;10(6):1445–1457. doi: 10.1002/j.1460-2075.1991.tb07665.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Tian J. M., Schibler U. Tissue-specific expression of the gene encoding hepatocyte nuclear factor 1 may involve hepatocyte nuclear factor 4. Genes Dev. 1991 Dec;5(12A):2225–2234. doi: 10.1101/gad.5.12a.2225. [DOI] [PubMed] [Google Scholar]
  31. Tsai S. F., Strauss E., Orkin S. H. Functional analysis and in vivo footprinting implicate the erythroid transcription factor GATA-1 as a positive regulator of its own promoter. Genes Dev. 1991 Jun;5(6):919–931. doi: 10.1101/gad.5.6.919. [DOI] [PubMed] [Google Scholar]
  32. Xanthopoulos K. G., Prezioso V. R., Chen W. S., Sladek F. M., Cortese R., Darnell J. E., Jr The different tissue transcription patterns of genes for HNF-1, C/EBP, HNF-3, and HNF-4, protein factors that govern liver-specific transcription. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3807–3811. doi: 10.1073/pnas.88.9.3807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. de Wet J. R., Wood K. V., DeLuca M., Helinski D. R., Subramani S. Firefly luciferase gene: structure and expression in mammalian cells. Mol Cell Biol. 1987 Feb;7(2):725–737. doi: 10.1128/mcb.7.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES