Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1987 Nov;7(11):4058–4064. doi: 10.1128/mcb.7.11.4058

Tissue-specific activity of the pro-opiomelanocortin gene promoter.

L Jeannotte 1, M A Trifiro 1, R K Plante 1, M Chamberland 1, J Drouin 1
PMCID: PMC368076  PMID: 3431549

Abstract

The pro-opiomelanocortin (POMC) gene is specifically expressed in corticotroph cells of the anterior pituitary. To define the POMC promoter sequences responsible for tissue-specific expression, we assessed POMC promoter activity by gene transfer into POMC-expressing pituitary tumor cells (AtT-20) and fibroblast L cells. The rat POMC promoter was only efficiently utilized and correctly transcribed in AtT-20 cells. 5'-End deletion analysis revealed two promoter regions required for activity in AtT-20 cells. When tested by fusion to a heterologous promoter, DNA fragments corresponding to both regions exhibited tissue-specific activity, suggesting the presence of at least two tissue-specific DNA sequence elements within the promoter. In summary, POMC promoter sequences from -480 to -34 base pairs appear sufficient to mimic the specificity of anterior pituitary expression.

Full text

PDF
4058

Images in this article

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. Boulet A. M., Erwin C. R., Rutter W. J. Cell-specific enhancers in the rat exocrine pancreas. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3599–3603. doi: 10.1073/pnas.83.11.3599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brinster R. L., Ritchie K. A., Hammer R. E., O'Brien R. L., Arp B., Storb U. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice. Nature. 1983 Nov 24;306(5941):332–336. doi: 10.1038/306332a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Catanzaro D. F., West B. L., Baxter J. D., Reudelhuber T. L. A pituitary-specific factor interacts with an upstream promotor element in the rat growth hormone gene. Mol Endocrinol. 1987 Jan;1(1):90–96. doi: 10.1210/mend-1-1-90. [DOI] [PubMed] [Google Scholar]
  5. Charron J., Drouin J. Glucocorticoid inhibition of transcription from episomal proopiomelanocortin gene promoter. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8903–8907. doi: 10.1073/pnas.83.23.8903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen C. L., Chang C. C., Krieger D. T., Bardin C. W. Expression and regulation of proopiomelanocortin-like gene in the ovary and placenta: comparison with the testis. Endocrinology. 1986 Jun;118(6):2382–2389. doi: 10.1210/endo-118-6-2382. [DOI] [PubMed] [Google Scholar]
  7. Chen C. L., Mather J. P., Morris P. L., Bardin C. W. Expression of pro-opiomelanocortin-like gene in the testis and epididymis. Proc Natl Acad Sci U S A. 1984 Sep;81(18):5672–5675. doi: 10.1073/pnas.81.18.5672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chepelinsky A. B., Sommer B., Piatigorsky J. Interaction between two different regulatory elements activates the murine alpha A-crystallin gene promoter in explanted lens epithelia. Mol Cell Biol. 1987 May;7(5):1807–1814. doi: 10.1128/mcb.7.5.1807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ciliberto G., Dente L., Cortese R. Cell-specific expression of a transfected human alpha 1-antitrypsin gene. Cell. 1985 Jun;41(2):531–540. doi: 10.1016/s0092-8674(85)80026-x. [DOI] [PubMed] [Google Scholar]
  10. Civelli O., Birnberg N., Herbert E. Detection and quantitation of pro-opiomelanocortin mRNA in pituitary and brain tissues from different species. J Biol Chem. 1982 Jun 25;257(12):6783–6787. [PubMed] [Google Scholar]
  11. Dhar R., McClements W. L., Enquist L. W., Vande Woude G. F. Nucleotide sequences of integrated Moloney sarcoma provirus long terminal repeats and their host and viral junctions. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3937–3941. doi: 10.1073/pnas.77.7.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Drouin J., Chamberland M., Charron J., Jeannotte L., Nemer M. Structure of the rat pro-opiomelanocortin (POMC) gene. FEBS Lett. 1985 Nov 25;193(1):54–58. doi: 10.1016/0014-5793(85)80078-8. [DOI] [PubMed] [Google Scholar]
  13. Edlund T., Walker M. D., Barr P. J., Rutter W. J. Cell-specific expression of the rat insulin gene: evidence for role of two distinct 5' flanking elements. Science. 1985 Nov 22;230(4728):912–916. doi: 10.1126/science.3904002. [DOI] [PubMed] [Google Scholar]
  14. Eipper B. A., Mains R. E. Structure and biosynthesis of pro-adrenocorticotropin/endorphin and related peptides. Endocr Rev. 1980 Winter;1(1):1–27. doi: 10.1210/edrv-1-1-1. [DOI] [PubMed] [Google Scholar]
  15. Flug F., Copp R. P., Casanova J., Horowitz Z. D., Janocko L., Plotnick M., Samuels H. H. cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J Biol Chem. 1987 May 5;262(13):6373–6382. [PubMed] [Google Scholar]
  16. Foster J., Stafford J., Queen C. An immunoglobulin promoter displays cell-type specificity independently of the enhancer. 1985 May 30-Jun 5Nature. 315(6018):423–425. doi: 10.1038/315423a0. [DOI] [PubMed] [Google Scholar]
  17. Gagner J. P., Drouin J. Opposite regulation of pro-opiomelanocortin gene transcription by glucocorticoids and CRH. Mol Cell Endocrinol. 1985 Apr;40(1):25–32. doi: 10.1016/0303-7207(85)90154-6. [DOI] [PubMed] [Google Scholar]
  18. Gee C. E., Chen C. L., Roberts J. L., Thompson R., Watson S. J. Identification of proopiomelanocortin neurones in rat hypothalamus by in situ cDNA-mRNA hybridization. Nature. 1983 Nov 24;306(5941):374–376. doi: 10.1038/306374a0. [DOI] [PubMed] [Google Scholar]
  19. Gillies S. D., Morrison S. L., Oi V. T., Tonegawa S. A tissue-specific transcription enhancer element is located in the major intron of a rearranged immunoglobulin heavy chain gene. Cell. 1983 Jul;33(3):717–728. doi: 10.1016/0092-8674(83)90014-4. [DOI] [PubMed] [Google Scholar]
  20. Gorman C. M., Merlino G. T., Willingham M. C., Pastan I., Howard B. H. The Rous sarcoma virus long terminal repeat is a strong promoter when introduced into a variety of eukaryotic cells by DNA-mediated transfection. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6777–6781. doi: 10.1073/pnas.79.22.6777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gross-Bellard M., Oudet P., Chambon P. Isolation of high-molecular-weight DNA from mammalian cells. Eur J Biochem. 1973 Jul 2;36(1):32–38. doi: 10.1111/j.1432-1033.1973.tb02881.x. [DOI] [PubMed] [Google Scholar]
  22. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  23. Israel A., Cohen S. N. Hormonally mediated negative regulation of human pro-opiomelanocortin gene expression after transfection into mouse L cells. Mol Cell Biol. 1985 Sep;5(9):2443–2453. doi: 10.1128/mcb.5.9.2443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  25. Laimins L. A., Tsichlis P., Khoury G. Multiple enhancer domains in the 3' terminus of the Prague strain of Rous sarcoma virus. Nucleic Acids Res. 1984 Aug 24;12(16):6427–6442. doi: 10.1093/nar/12.16.6427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lefevre C., Imagawa M., Dana S., Grindlay J., Bodner M., Karin M. Tissue-specific expression of the human growth hormone gene is conferred in part by the binding of a specific trans-acting factor. EMBO J. 1987 Apr;6(4):971–981. doi: 10.1002/j.1460-2075.1987.tb04847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lok S., Breitman M. L., Chepelinsky A. B., Piatigorsky J., Gold R. J., Tsui L. C. Lens-specific promoter activity of a mouse gamma-crystallin gene. Mol Cell Biol. 1985 Sep;5(9):2221–2230. doi: 10.1128/mcb.5.9.2221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Mason J. O., Williams G. T., Neuberger M. S. Transcription cell type specificity is conferred by an immunoglobulin VH gene promoter that includes a functional consensus sequence. Cell. 1985 Jun;41(2):479–487. doi: 10.1016/s0092-8674(85)80021-0. [DOI] [PubMed] [Google Scholar]
  29. McKnight S. L., Gavis E. R., Kingsbury R., Axel R. Analysis of transcriptional regulatory signals of the HSV thymidine kinase gene: identification of an upstream control region. Cell. 1981 Aug;25(2):385–398. doi: 10.1016/0092-8674(81)90057-x. [DOI] [PubMed] [Google Scholar]
  30. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  31. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mishina M., Kurosaki T., Yamamoto T., Notake M., Masu M., Numa S. DNA sequences required for transcription in vivo of the human corticotropin-beta-lipotropin precursor gene. EMBO J. 1982;1(12):1533–1538. doi: 10.1002/j.1460-2075.1982.tb01351.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nelson C., Crenshaw E. B., 3rd, Franco R., Lira S. A., Albert V. R., Evans R. M., Rosenfeld M. G. Discrete cis-active genomic sequences dictate the pituitary cell type-specific expression of rat prolactin and growth hormone genes. Nature. 1986 Aug 7;322(6079):557–562. doi: 10.1038/322557a0. [DOI] [PubMed] [Google Scholar]
  34. Neuberger M. S. Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. EMBO J. 1983;2(8):1373–1378. doi: 10.1002/j.1460-2075.1983.tb01594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ondek B., Shepard A., Herr W. Discrete elements within the SV40 enhancer region display different cell-specific enhancer activities. EMBO J. 1987 Apr;6(4):1017–1025. doi: 10.1002/j.1460-2075.1987.tb04854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Overbeek P. A., Chepelinsky A. B., Khillan J. S., Piatigorsky J., Westphal H. Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815–7819. doi: 10.1073/pnas.82.23.7815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Parslow T. G., Jones S. D., Bond B., Yamamoto K. R. The immunoglobulin octanucleotide: independent activity and selective interaction with enhancers. Science. 1987 Mar 20;235(4795):1498–1501. doi: 10.1126/science.3029871. [DOI] [PubMed] [Google Scholar]
  38. Potter H., Weir L., Leder P. Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7161–7165. doi: 10.1073/pnas.81.22.7161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  41. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  42. Swift G. H., Hammer R. E., MacDonald R. J., Brinster R. L. Tissue-specific expression of the rat pancreatic elastase I gene in transgenic mice. Cell. 1984 Oct;38(3):639–646. doi: 10.1016/0092-8674(84)90258-7. [DOI] [PubMed] [Google Scholar]
  43. Walker M. D., Edlund T., Boulet A. M., Rutter W. J. Cell-specific expression controlled by the 5'-flanking region of insulin and chymotrypsin genes. Nature. 1983 Dec 8;306(5943):557–561. doi: 10.1038/306557a0. [DOI] [PubMed] [Google Scholar]
  44. West B. L., Catanzaro D. F., Mellon S. H., Cattini P. A., Baxter J. D., Reudelhuber T. L. Interaction of a tissue-specific factor with an essential rat growth hormone gene promoter element. Mol Cell Biol. 1987 Mar;7(3):1193–1197. doi: 10.1128/mcb.7.3.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wu L. C., Morley B. J., Campbell R. D. Cell-specific expression of the human complement protein factor B gene: evidence for the role of two distinct 5'-flanking elements. Cell. 1987 Jan 30;48(2):331–342. doi: 10.1016/0092-8674(87)90436-3. [DOI] [PubMed] [Google Scholar]
  46. Ye Z. S., Samuels H. H. Cell- and sequence-specific binding of nuclear proteins to 5'-flanking DNA of the rat growth hormone gene. J Biol Chem. 1987 May 5;262(13):6313–6317. [PubMed] [Google Scholar]
  47. 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]

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

RESOURCES