Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Nov 1;24(21):4185–4191. doi: 10.1093/nar/24.21.4185

Characterization of the rat Class 3 aldehyde dehydrogenase gene promoter.

Y Q Xie 1, K Takimoto 1, H C Pitot 1, W K Miskimins 1, R Lindahl 1
PMCID: PMC146258  PMID: 8932370

Abstract

The Class 3 aldehyde dehydrogenase gene (ALDH-3) is differentially expressed. Expression is either constitutive or xenobiotic inducible via an aromatic hydrocarbon (Ah) receptor-mediated pathway, depending upon the tissue. A series of studies were performed to examine the regulation of rat ALDH-3 basal expression. DNase I footprint analysis identified four DNA regions within the proximal 1 kb of the 5' flanking region of rat ALDH-3 which interact with regulatory proteins. Reporter gene and gel mobility shift assays indicate that Sp1-like proteins interact with two proximal DNase I footprinted sites to confer strong promoter activity. Two distal DNase I footprinted sites are found within a region that inhibits rat ALDH-3 promoter activity. This negative region is bound by NF1-like proteins and/or unique proteins. This 1 kb 5' flanking region of rat ALDH-3 may act constitutively in many cell types. In contrast with other Ah receptor regulated genes, no DNA elements or transcription factors acting within this region appear to be involved in regulating xenobiotic-inducible expression of rat ALDH-3.

Full Text

The Full Text of this article is available as a PDF (168.8 KB).

Selected References

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

  1. Asman D. C., Takimoto K., Pitot H. C., Dunn T. J., Lindahl R. Organization and characterization of the rat class 3 aldehyde dehydrogenase gene. J Biol Chem. 1993 Jun 15;268(17):12530–12536. [PubMed] [Google Scholar]
  2. Boesch J. S., Lee C., Lindahl R. G. Constitutive expression of class 3 aldehyde dehydrogenase in cultured rat corneal epithelium. J Biol Chem. 1996 Mar 1;271(9):5150–5157. doi: 10.1074/jbc.271.9.5150. [DOI] [PubMed] [Google Scholar]
  3. Bresser J., Doering J., Gillespie D. Quick-blot: selective mRNA or DNA immobilization from whole cells. DNA. 1983;2(3):243–254. doi: 10.1089/dna.1983.2.243. [DOI] [PubMed] [Google Scholar]
  4. Campbell P., Irving C. C., Lindahl R. Changes in aldehyde dehydrogenase during rat urinary bladder carcinogenesis. Carcinogenesis. 1989 Nov;10(11):2081–2087. doi: 10.1093/carcin/10.11.2081. [DOI] [PubMed] [Google Scholar]
  5. Carlstedt-Duke J. M. Tissue distribution of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat. Cancer Res. 1979 Aug;39(8):3172–3176. [PubMed] [Google Scholar]
  6. Colantuoni V., Pirozzi A., Blance C., Cortese R. Negative control of liver-specific gene expression: cloned human retinol-binding protein gene is repressed in HeLa cells. EMBO J. 1987 Mar;6(3):631–636. doi: 10.1002/j.1460-2075.1987.tb04801.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dunn T. J., Koleske A. J., Lindahl R., Pitot H. C. Phenobarbital-inducible aldehyde dehydrogenase in the rat. cDNA sequence and regulation of the mRNA by phenobarbital in responsive rats. J Biol Chem. 1989 Aug 5;264(22):13057–13065. [PubMed] [Google Scholar]
  9. Dunn T. J., Lindahl R., Pitot H. C. Differential gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Noncoordinate regulation of a TCDD-induced aldehyde dehydrogenase and cytochrome P-450c in the rat. J Biol Chem. 1988 Aug 5;263(22):10878–10886. [PubMed] [Google Scholar]
  10. Elferink C. J., Whitlock J. P., Jr Dioxin-dependent, DNA sequence-specific binding of a multiprotein complex containing the Ah receptor. Receptor. 1994 Fall;4(3):157–173. [PubMed] [Google Scholar]
  11. Evces S., Lindahl R. Characterization of rat cornea aldehyde dehydrogenase. Arch Biochem Biophys. 1989 Nov 1;274(2):518–524. doi: 10.1016/0003-9861(89)90465-7. [DOI] [PubMed] [Google Scholar]
  12. Faisst S., Meyer S. Compilation of vertebrate-encoded transcription factors. Nucleic Acids Res. 1992 Jan 11;20(1):3–26. doi: 10.1093/nar/20.1.3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gil G., Smith J. R., Goldstein J. L., Slaughter C. A., Orth K., Brown M. S., Osborne T. F. Multiple genes encode nuclear factor 1-like proteins that bind to the promoter for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8963–8967. doi: 10.1073/pnas.85.23.8963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gonzalez F. J., Nebert D. W. Autoregulation plus upstream positive and negative control regions associated with transcriptional activation of the mouse P1(450) gene. Nucleic Acids Res. 1985 Oct 25;13(20):7269–7288. doi: 10.1093/nar/13.20.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goyal N., Knox J., Gronostajski R. M. Analysis of multiple forms of nuclear factor I in human and murine cell lines. Mol Cell Biol. 1990 Mar;10(3):1041–1048. doi: 10.1128/mcb.10.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hines R. N., Mathis J. M., Jacob C. S. Identification of multiple regulatory elements on the human cytochrome P450IA1 gene. Carcinogenesis. 1988 Sep;9(9):1599–1605. doi: 10.1093/carcin/9.9.1599. [DOI] [PubMed] [Google Scholar]
  17. Hirsch S., Miskimins W. K. Mitogen induction of nuclear factors that interact with a delayed responsive region of the transferrin receptor gene promoter. Cell Growth Differ. 1995 Jun;6(6):719–726. [PubMed] [Google Scholar]
  18. Hsu L. C., Chang W. C., Shibuya A., Yoshida A. Human stomach aldehyde dehydrogenase cDNA and genomic cloning, primary structure, and expression in Escherichia coli. J Biol Chem. 1992 Feb 15;267(5):3030–3037. [PubMed] [Google Scholar]
  19. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  20. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  21. Lin K. H., Brennan M. D., Lindahl R. Expression of tumor-associated aldehyde dehydrogenase gene in rat hepatoma cell lines. Cancer Res. 1988 Dec 15;48(24 Pt 1):7009–7012. [PubMed] [Google Scholar]
  22. Lindahl R. Aldehyde dehydrogenases and their role in carcinogenesis. Crit Rev Biochem Mol Biol. 1992;27(4-5):283–335. doi: 10.3109/10409239209082565. [DOI] [PubMed] [Google Scholar]
  23. McKnight S. L., Kingsbury R. C., Spence A., Smith M. The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence. Cell. 1984 May;37(1):253–262. doi: 10.1016/0092-8674(84)90321-0. [DOI] [PubMed] [Google Scholar]
  24. Nagata K., Guggenheimer R. A., Hurwitz J. Specific binding of a cellular DNA replication protein to the origin of replication of adenovirus DNA. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6177–6181. doi: 10.1073/pnas.80.20.6177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Paige C. J., Kincade P. W., Ralph P. Independent control of immunoglobulin heavy and light chain expression in a murine pre-B-cell line. Nature. 1981 Aug 13;292(5824):631–633. doi: 10.1038/292631a0. [DOI] [PubMed] [Google Scholar]
  26. Postel E. H., Mango S. E., Flint S. J. A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor. Mol Cell Biol. 1989 Nov;9(11):5123–5133. doi: 10.1128/mcb.9.11.5123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rossi P., Karsenty G., Roberts A. B., Roche N. S., Sporn M. B., de Crombrugghe B. A nuclear factor 1 binding site mediates the transcriptional activation of a type I collagen promoter by transforming growth factor-beta. Cell. 1988 Feb 12;52(3):405–414. doi: 10.1016/s0092-8674(88)80033-3. [DOI] [PubMed] [Google Scholar]
  28. Sogawa K., Nakano R., Kobayashi A., Kikuchi Y., Ohe N., Matsushita N., Fujii-Kuriyama Y. Possible function of Ah receptor nuclear translocator (Arnt) homodimer in transcriptional regulation. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1936–1940. doi: 10.1073/pnas.92.6.1936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Takimoto K., Lindahl R., Dunn T. J., Pitot H. C. Structure of the 5' flanking region of class 3 aldehyde dehydrogenase in the rat. Arch Biochem Biophys. 1994 Aug 1;312(2):539–546. doi: 10.1006/abbi.1994.1343. [DOI] [PubMed] [Google Scholar]
  30. Takimoto K., Lindahl R., Pitot H. C. Regulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase in hepatoma cells. Arch Biochem Biophys. 1992 Nov 1;298(2):493–497. doi: 10.1016/0003-9861(92)90440-8. [DOI] [PubMed] [Google Scholar]
  31. Takimoto K., Lindahl R., Pitot H. C. Superinduction of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible expression of aldehyde dehydrogenase by the inhibition of protein synthesis. Biochem Biophys Res Commun. 1991 Oct 31;180(2):953–959. doi: 10.1016/s0006-291x(05)81158-1. [DOI] [PubMed] [Google Scholar]
  32. Törrönen R., Nousiainen U., Hänninen O. Induction of aldehyde dehydrogenase by polycyclic aromatic hydrocarbons in rats. Chem Biol Interact. 1981 Jul;36(1):33–44. doi: 10.1016/0009-2797(81)90027-2. [DOI] [PubMed] [Google Scholar]
  33. Vasiliou V., Puga A., Chang C. Y., Tabor M. W., Nebert D. W. Interaction between the Ah receptor and proteins binding to the AP-1-like electrophile response element (EpRE) during murine phase II [Ah] battery gene expression. Biochem Pharmacol. 1995 Dec 22;50(12):2057–2068. doi: 10.1016/0006-2952(95)02108-6. [DOI] [PubMed] [Google Scholar]
  34. Vasiliou V., Shertzer H. G., Liu R. M., Sainsbury M., Nebert D. W. Response of [Ah] battery genes to compounds that protect against menadione toxicity. Biochem Pharmacol. 1995 Nov 27;50(11):1885–1891. doi: 10.1016/0006-2952(95)02083-7. [DOI] [PubMed] [Google Scholar]
  35. Wigler M., Pellicer A., Silverstein S., Axel R. Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell. 1978 Jul;14(3):725–731. doi: 10.1016/0092-8674(78)90254-4. [DOI] [PubMed] [Google Scholar]
  36. Yin S. J., Liao C. S., Wang S. L., Chen Y. J., Wu C. W. Kinetic evidence for human liver and stomach aldehyde dehydrogenase-3 representing an unique class of isozymes. Biochem Genet. 1989 Jun;27(5-6):321–331. doi: 10.1007/BF00554167. [DOI] [PubMed] [Google Scholar]

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

RESOURCES