Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 Dec;7(12):4329–4336. doi: 10.1128/mcb.7.12.4329

Cell-specific expression of the human gastrin gene: evidence for a control element located downstream of the TATA box.

L E Theill 1, O Wiborg 1, J Vuust 1
PMCID: PMC368116  PMID: 2830490

Abstract

Fragments of 5'-flanking and noncoding exon I sequences of the human gastrin gene were analyzed in transient expression assays after transfection of a variety of cell lines with the pSVCAT vector system. In the presence of the simian virus 40 (SV40) enhancer, the gastrin gene fragment from nucleotides -250 to +57, relative to the cap site, was as efficient a promoter as the SV40 early promoter itself. In the absence of the SV40 enhancer, gastrin gene 5'-flanking sequences had no promoter activity except in the murine neuroblastoma cell line N18TG2. In this cell line, the fragment from -1300 to +57 stimulated transcription as actively as the SV40 early promoter with its enhancer. This cell-specific gastrin gene promoter activity was in accordance with the finding that gastrin is synthesized in certain neuronal cells. Promoter activity declined with decreasing distance from the 5' end to the cap site and disappeared after removal of the gastrin gene TATA box. In vector constructions containing short vector-linker sequences homologous to a functionally important region of the SV40 enhancer, the gastrin gene fragment from -17 to +57 showed considerable promoter activity, exclusively in N18TG2. It is concluded that the truncated gastrin gene promoter plus the first exon contains a cell-specific element that may act in collaboration with upstream elements to facilitate the accumulation of transcripts.

Full text

PDF
4329

Images in this article

4333Image
on p.4333
4334Image
on p.4334

Selected References

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

  1. Banerji J., Olson L., Schaffner W. A lymphocyte-specific cellular enhancer is located downstream of the joining region in immunoglobulin heavy chain genes. Cell. 1983 Jul;33(3):729–740. doi: 10.1016/0092-8674(83)90015-6. [DOI] [PubMed] [Google Scholar]
  2. Boel E., Vuust J., Norris F., Norris K., Wind A., Rehfeld J. F., Marcker K. A. Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc Natl Acad Sci U S A. 1983 May;80(10):2866–2869. doi: 10.1073/pnas.80.10.2866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Charnay P., Treisman R., Mellon P., Chao M., Axel R., Maniatis T. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences. Cell. 1984 Aug;38(1):251–263. doi: 10.1016/0092-8674(84)90547-6. [DOI] [PubMed] [Google Scholar]
  4. Chen I. S. Regulation of AIDS virus expression. Cell. 1986 Oct 10;47(1):1–2. doi: 10.1016/0092-8674(86)90359-4. [DOI] [PubMed] [Google Scholar]
  5. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  6. Derse D., Caradonna S. J., Casey J. W. Bovine leukemia virus long terminal repeat: a cell type-specific promoter. Science. 1985 Jan 18;227(4684):317–320. doi: 10.1126/science.2981431. [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. Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
  9. Herr W., Clarke J. The SV40 enhancer is composed of multiple functional elements that can compensate for one another. Cell. 1986 May 9;45(3):461–470. doi: 10.1016/0092-8674(86)90332-6. [DOI] [PubMed] [Google Scholar]
  10. Herr W., Gluzman Y. Duplications of a mutated simian virus 40 enhancer restore its activity. Nature. 1985 Feb 21;313(6004):711–714. doi: 10.1038/313711a0. [DOI] [PubMed] [Google Scholar]
  11. Hollingsworth M. J., Johanningmeier U., Karabin G. D., Stiegler G. L., Hallick R. B. Detection of multiple, unspliced precursor mRNA transcripts for the Mr 32,000 thylakoid membrane protein from Euglena gracilis chloroplasts. Nucleic Acids Res. 1984 Feb 24;12(4):2001–2017. doi: 10.1093/nar/12.4.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hökfelt T., Lundberg J. M., Tatemoto K., Mutt V., Terenius L., Polak J., Bloom S., Sasek C., Elde R., Goldstein M. Neuropeptide Y (NPY)- and FMRFamide neuropeptide-like immunoreactivities in catecholamine neurons of the rat medulla oblongata. Acta Physiol Scand. 1983 Feb;117(2):315–318. doi: 10.1111/j.1748-1716.1983.tb07214.x. [DOI] [PubMed] [Google Scholar]
  13. Ito R., Sato K., Helmer T., Jay G., Agarwal K. Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4662–4666. doi: 10.1073/pnas.81.15.4662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jones K. A., Kadonaga J. T., Luciw P. A., Tjian R. Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1. Science. 1986 May 9;232(4751):755–759. doi: 10.1126/science.3008338. [DOI] [PubMed] [Google Scholar]
  15. Jones K. A., Tjian R. Sp1 binds to promoter sequences and activates herpes simplex virus 'immediate-early' gene transcription in vitro. Nature. 1985 Sep 12;317(6033):179–182. doi: 10.1038/317179a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Kohl N. E., Gee C. E., Alt F. W. Activated expression of the N-myc gene in human neuroblastomas and related tumors. Science. 1984 Dec 14;226(4680):1335–1337. doi: 10.1126/science.6505694. [DOI] [PubMed] [Google Scholar]
  18. Mansour S. L., Grodzicker T., Tjian R. Downstream sequences affect transcription initiation from the adenovirus major late promoter. Mol Cell Biol. 1986 Jul;6(7):2684–2694. doi: 10.1128/mcb.6.7.2684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McKinnon R. D., Shinnick T. M., Sutcliffe J. G. The neuronal identifier element is a cis-acting positive regulator of gene expression. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3751–3755. doi: 10.1073/pnas.83.11.3751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Merrill G. F., Hauschka S. D., McKnight S. L. tk Enzyme expression in differentiating muscle cells is regulated through an internal segment of the cellular tk gene. Mol Cell Biol. 1984 Sep;4(9):1777–1784. doi: 10.1128/mcb.4.9.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Minna J., Glazer D., Nirenberg M. Genetic dissection of neural properties using somatic cell hybrids. Nat New Biol. 1972 Feb 23;235(60):225–231. doi: 10.1038/newbio235225a0. [DOI] [PubMed] [Google Scholar]
  23. Minth C. D., Bloom S. R., Polak J. M., Dixon J. E. Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4577–4581. doi: 10.1073/pnas.81.14.4577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Muesing M. A., Smith D. H., Capon D. J. Regulation of mRNA accumulation by a human immunodeficiency virus trans-activator protein. Cell. 1987 Feb 27;48(4):691–701. doi: 10.1016/0092-8674(87)90247-9. [DOI] [PubMed] [Google Scholar]
  25. Nelson P., Ruffner W., Nirenberg M. Neuronal tumor cells with excitable membranes grown in vitro. Proc Natl Acad Sci U S A. 1969 Nov;64(3):1004–1010. doi: 10.1073/pnas.64.3.1004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ohtani K., Nakamura M., Saito S., Noda T., Ito Y., Sugamura K., Hinuma Y. Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression. EMBO J. 1987 Feb;6(2):389–395. doi: 10.1002/j.1460-2075.1987.tb04767.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Paek I., Axel R. Glucocorticoids enhance stability of human growth hormone mRNA. Mol Cell Biol. 1987 Apr;7(4):1496–1507. doi: 10.1128/mcb.7.4.1496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Powell C. T., Ney C., Aran P., Agarwal K. A gastrin gene is expressed in both porcine pituitary and antral mucosal tissues. Nucleic Acids Res. 1985 Oct 25;13(20):7299–7305. doi: 10.1093/nar/13.20.7299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Queen C., Baltimore D. Immunoglobulin gene transcription is activated by downstream sequence elements. Cell. 1983 Jul;33(3):741–748. doi: 10.1016/0092-8674(83)90016-8. [DOI] [PubMed] [Google Scholar]
  30. Reeve J. R., Jr, Walsh J. H., Tompkins R. K., Hawke D., Shively J. E. Amino terminal fragments of human progastrin from gastrinoma. Biochem Biophys Res Commun. 1984 Aug 30;123(1):404–409. doi: 10.1016/0006-291x(84)90428-5. [DOI] [PubMed] [Google Scholar]
  31. Rehfeld J. F. Accumulation of nonamidated preprogastrin and preprocholecystokinin products in porcine pituitary corticotrophs. Evidence of post-translational control of cell differentiation. J Biol Chem. 1986 May 5;261(13):5841–5847. [PubMed] [Google Scholar]
  32. Rehfeld J. F. Localisation of gastrins to neuro- and adenohypophysis. Nature. 1978 Feb 23;271(5647):771–773. doi: 10.1038/271771a0. [DOI] [PubMed] [Google Scholar]
  33. Rosen C. A., Sodroski J. G., Haseltine W. A. The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell. 1985 Jul;41(3):813–823. doi: 10.1016/s0092-8674(85)80062-3. [DOI] [PubMed] [Google Scholar]
  34. Schirm S., Jiricny J., Schaffner W. The SV40 enhancer can be dissected into multiple segments, each with a different cell type specificity. Genes Dev. 1987 Mar;1(1):65–74. doi: 10.1101/gad.1.1.65. [DOI] [PubMed] [Google Scholar]
  35. Schwab M., Alitalo K., Klempnauer K. H., Varmus H. E., Bishop J. M., Gilbert F., Brodeur G., Goldstein M., Trent J. Amplified DNA with limited homology to myc cellular oncogene is shared by human neuroblastoma cell lines and a neuroblastoma tumour. Nature. 1983 Sep 15;305(5931):245–248. doi: 10.1038/305245a0. [DOI] [PubMed] [Google Scholar]
  36. Singh P., Walker J. P., Townsend C. M., Jr, Thompson J. C. Role of gastrin and gastrin receptors on the growth of a transplantable mouse colon carcinoma (MC-26) in BALB/c mice. Cancer Res. 1986 Apr;46(4 Pt 1):1612–1616. [PubMed] [Google Scholar]
  37. Takahashi Y., Fukushige S., Murotsu T., Matsubara K. Structure of human cholecystokinin gene and its chromosomal location. Gene. 1986;50(1-3):353–360. doi: 10.1016/0378-1119(86)90339-2. [DOI] [PubMed] [Google Scholar]
  38. Tinoco I., Jr, Borer P. N., Dengler B., Levin M. D., Uhlenbeck O. C., Crothers D. M., Bralla J. Improved estimation of secondary structure in ribonucleic acids. Nat New Biol. 1973 Nov 14;246(150):40–41. doi: 10.1038/newbio246040a0. [DOI] [PubMed] [Google Scholar]
  39. Uvnäs-Wallensten K., Rehfeld J. F., Larsson L. I., Uvnäs B. Heptadecapeptide gastrin in the vagal nerve. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5707–5710. doi: 10.1073/pnas.74.12.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Uvnäs-Wallensten K., Uvnäs B. Release of gastrin on stimulation of the sciatic and brachial nerves of the cat. Acta Physiol Scand. 1978 Jul;103(3):349–351. doi: 10.1111/j.1748-1716.1978.tb06226.x. [DOI] [PubMed] [Google Scholar]
  41. Wiborg O., Berglund L., Boel E., Norris F., Norris K., Rehfeld J. F., Marcker K. A., Vuust J. Structure of a human gastrin gene. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1067–1069. doi: 10.1073/pnas.81.4.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Yeats J. C., Allen J. M., Bloom S. R., Leigh P. J., MacDermot J. Neuropeptide Y in neuroblastoma X glioma hybrid cells. Response to dexamethasone and nerve growth factor. FEBS Lett. 1983 Oct 31;163(1):57–61. doi: 10.1016/0014-5793(83)81162-4. [DOI] [PubMed] [Google Scholar]
  43. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES