Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Jun 15;26(12):3018–3025. doi: 10.1093/nar/26.12.3018

Unique organization and involvement of GAGA factors in transcriptional regulation of the Xenopus stromelysin-3 gene.

J Li 1, V C Liang 1, T Sedgwick 1, J Wong 1, Y B Shi 1
PMCID: PMC147655  PMID: 9611250

Abstract

Expression of the matrix metalloproteinase (MMP) gene stromelysin-3 ( ST3 ) has been shown to be tightly associated with cell migration and apoptosis inmammals and amphibians. This contrasts with most other MMP genes. We demonstrate here that the Xenopus ST3 gene also has a structure distinct from other MMP genes, with its C-terminal half (the hemopexin domain) encoded by 4 instead of 6 exons, as in other MMP genes. Our primer extension analysis reveals the existence of two transcription start sites and at least one is needed for transcription of the promoter in transient transfection assays. Furthermore, our deletion analysis has demonstrated a requirement for at least one GAGA factor binding site for promoter function. In vitro DNA binding and mutational studies have provided strong evidence for the participation of GAGA or GAGA-like factors in transcriptional regulation of the frog ST3 gene. This contrasts with regulation of the human ST3 promoter. These results suggest that the ST3 gene evolved prior to most other metalloproteinase genes and uses distinct regulation pathways to achieve similar expression profiles and serve similar functions in mammals and amphibians.

Full Text

The Full Text of this article is available as a PDF (358.3 KB).

Selected References

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

  1. Anglard P., Melot T., Guérin E., Thomas G., Basset P. Structure and promoter characterization of the human stromelysin-3 gene. J Biol Chem. 1995 Sep 1;270(35):20337–20344. doi: 10.1074/jbc.270.35.20337. [DOI] [PubMed] [Google Scholar]
  2. Anizet M. P., Huwe B., Pays A., Picard J. J. Characterization of a new cell line, XL2, obtained from Xenopus laevis and determination of optimal culture conditions. In Vitro. 1981 Apr;17(4):267–274. doi: 10.1007/BF02618137. [DOI] [PubMed] [Google Scholar]
  3. Basset P., Bellocq J. P., Wolf C., Stoll I., Hutin P., Limacher J. M., Podhajcer O. L., Chenard M. P., Rio M. C., Chambon P. A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas. Nature. 1990 Dec 20;348(6303):699–704. doi: 10.1038/348699a0. [DOI] [PubMed] [Google Scholar]
  4. Birkedal-Hansen H., Moore W. G., Bodden M. K., Windsor L. J., Birkedal-Hansen B., DeCarlo A., Engler J. A. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993;4(2):197–250. doi: 10.1177/10454411930040020401. [DOI] [PubMed] [Google Scholar]
  5. Boudreau N., Sympson C. J., Werb Z., Bissell M. J. Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix. Science. 1995 Feb 10;267(5199):891–893. doi: 10.1126/science.7531366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Breathnach R., Matrisian L. M., Gesnel M. C., Staub A., Leroy P. Sequences coding for part of oncogene-induced transin are highly conserved in a related rat gene. Nucleic Acids Res. 1987 Feb 11;15(3):1139–1151. doi: 10.1093/nar/15.3.1139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Collier I. E., Bruns G. A., Goldberg G. I., Gerhard D. S. On the structure and chromosome location of the 72- and 92-kDa human type IV collagenase genes. Genomics. 1991 Mar;9(3):429–434. doi: 10.1016/0888-7543(91)90408-7. [DOI] [PubMed] [Google Scholar]
  8. Collier I. E., Smith J., Kronberger A., Bauer E. A., Wilhelm S. M., Eisen A. Z., Goldberg G. I. The structure of the human skin fibroblast collagenase gene. J Biol Chem. 1988 Aug 5;263(22):10711–10713. [PubMed] [Google Scholar]
  9. Fini M. E., Plucinska I. M., Mayer A. S., Gross R. H., Brinckerhoff C. E. A gene for rabbit synovial cell collagenase: member of a family of metalloproteinases that degrade the connective tissue matrix. Biochemistry. 1987 Sep 22;26(19):6156–6165. doi: 10.1021/bi00393a032. [DOI] [PubMed] [Google Scholar]
  10. Gaire M., Magbanua Z., McDonnell S., McNeil L., Lovett D. H., Matrisian L. M. Structure and expression of the human gene for the matrix metalloproteinase matrilysin. J Biol Chem. 1994 Jan 21;269(3):2032–2040. [PubMed] [Google Scholar]
  11. Granok H., Leibovitch B. A., Shaffer C. D., Elgin S. C. Chromatin. Ga-ga over GAGA factor. Curr Biol. 1995 Mar 1;5(3):238–241. doi: 10.1016/s0960-9822(95)00048-0. [DOI] [PubMed] [Google Scholar]
  12. Gross J. How tadpoles lose their tails. J Invest Dermatol. 1966 Oct;47(4):274–277. [PubMed] [Google Scholar]
  13. Herrin D. L., Schmidt G. W. Rapid, reversible staining of northern blots prior to hybridization. Biotechniques. 1988 Mar;6(3):196-7, 199-200. [PubMed] [Google Scholar]
  14. Huhtala P., Chow L. T., Tryggvason K. Structure of the human type IV collagenase gene. J Biol Chem. 1990 Jul 5;265(19):11077–11082. [PubMed] [Google Scholar]
  15. Huhtala P., Tuuttila A., Chow L. T., Lohi J., Keski-Oja J., Tryggvason K. Complete structure of the human gene for 92-kDa type IV collagenase. Divergent regulation of expression for the 92- and 72-kilodalton enzyme genes in HT-1080 cells. J Biol Chem. 1991 Sep 5;266(25):16485–16490. [PubMed] [Google Scholar]
  16. Ishizuya-Oka A., Ueda S., Shi Y. B. Transient expression of stromelysin-3 mRNA in the amphibian small intestine during metamorphosis. Cell Tissue Res. 1996 Feb;283(2):325–329. doi: 10.1007/s004410050542. [DOI] [PubMed] [Google Scholar]
  17. Kleiner D. E., Jr, Stetler-Stevenson W. G. Structural biochemistry and activation of matrix metalloproteases. Curr Opin Cell Biol. 1993 Oct;5(5):891–897. doi: 10.1016/0955-0674(93)90040-w. [DOI] [PubMed] [Google Scholar]
  18. Lefebvre O., Wolf C., Limacher J. M., Hutin P., Wendling C., LeMeur M., Basset P., Rio M. C. The breast cancer-associated stromelysin-3 gene is expressed during mouse mammary gland apoptosis. J Cell Biol. 1992 Nov;119(4):997–1002. doi: 10.1083/jcb.119.4.997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lund L. R., Rømer J., Thomasset N., Solberg H., Pyke C., Bissell M. J., Danø K., Werb Z. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways. Development. 1996 Jan;122(1):181–193. doi: 10.1242/dev.122.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matrisian L. M. The matrix-degrading metalloproteinases. Bioessays. 1992 Jul;14(7):455–463. doi: 10.1002/bies.950140705. [DOI] [PubMed] [Google Scholar]
  21. Miller L., Daniel J. C. Comparison of in vivo and in vitro ribosomal RNA synthesis in nucleolar mutants of Xenopus laevis. In Vitro. 1977 Sep;13(9):557–563. doi: 10.1007/BF02627851. [DOI] [PubMed] [Google Scholar]
  22. Murphy G., Willenbrock F., Crabbe T., O'Shea M., Ward R., Atkinson S., O'Connell J., Docherty A. Regulation of matrix metalloproteinase activity. Ann N Y Acad Sci. 1994 Sep 6;732:31–41. doi: 10.1111/j.1749-6632.1994.tb24722.x. [DOI] [PubMed] [Google Scholar]
  23. Nagase H., Suzuki K., Morodomi T., Enghild J. J., Salvesen G. Activation mechanisms of the precursors of matrix metalloproteinases 1, 2 and 3. Matrix Suppl. 1992;1:237–244. [PubMed] [Google Scholar]
  24. Oofusa K., Yomori S., Yoshizato K. Regionally and hormonally regulated expression of genes of collagen and collagenase in the anuran larval skin. Int J Dev Biol. 1994 Jun;38(2):345–350. [PubMed] [Google Scholar]
  25. Patterton D., Hayes W. P., Shi Y. B. Transcriptional activation of the matrix metalloproteinase gene stromelysin-3 coincides with thyroid hormone-induced cell death during frog metamorphosis. Dev Biol. 1995 Jan;167(1):252–262. doi: 10.1006/dbio.1995.1021. [DOI] [PubMed] [Google Scholar]
  26. Pei D., Weiss S. J. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature. 1995 May 18;375(6528):244–247. doi: 10.1038/375244a0. [DOI] [PubMed] [Google Scholar]
  27. Puzianowska-Kuznicka M., Wong J., Kanamori A., Shi Y. B. Functional characterization of a mutant thyroid hormone receptor in Xenopus laevis. J Biol Chem. 1996 Dec 27;271(52):33394–33403. doi: 10.1074/jbc.271.52.33394. [DOI] [PubMed] [Google Scholar]
  28. Ranjan M., Wong J., Shi Y. B. Transcriptional repression of Xenopus TR beta gene is mediated by a thyroid hormone response element located near the start site. J Biol Chem. 1994 Oct 7;269(40):24699–24705. [PubMed] [Google Scholar]
  29. Roeder R. G. The complexities of eukaryotic transcription initiation: regulation of preinitiation complex assembly. Trends Biochem Sci. 1991 Nov;16(11):402–408. doi: 10.1016/0968-0004(91)90164-q. [DOI] [PubMed] [Google Scholar]
  30. Ruoslahti E., Reed J. C. Anchorage dependence, integrins, and apoptosis. Cell. 1994 May 20;77(4):477–478. doi: 10.1016/0092-8674(94)90209-7. [DOI] [PubMed] [Google Scholar]
  31. Sang Q. A., Douglas D. A. Computational sequence analysis of matrix metalloproteinases. J Protein Chem. 1996 Feb;15(2):137–160. doi: 10.1007/BF01887395. [DOI] [PubMed] [Google Scholar]
  32. Sato H., Seiki M. Membrane-type matrix metalloproteinases (MT-MMPs) in tumor metastasis. J Biochem. 1996 Feb;119(2):209–215. doi: 10.1093/oxfordjournals.jbchem.a021223. [DOI] [PubMed] [Google Scholar]
  33. Shi Y. B., Hayes W. P. Thyroid hormone-dependent regulation of the intestinal fatty acid-binding protein gene during amphibian metamorphosis. Dev Biol. 1994 Jan;161(1):48–58. doi: 10.1006/dbio.1994.1006. [DOI] [PubMed] [Google Scholar]
  34. Shi Y. B., Ishizuya-Oka A. Biphasic intestinal development in amphibians: embryogenesis and remodeling during metamorphosis. Curr Top Dev Biol. 1996;32:205–235. doi: 10.1016/s0070-2153(08)60429-9. [DOI] [PubMed] [Google Scholar]
  35. Shi Y. B., Yaoita Y., Brown D. D. Genomic organization and alternative promoter usage of the two thyroid hormone receptor beta genes in Xenopus laevis. J Biol Chem. 1992 Jan 15;267(2):733–738. [PubMed] [Google Scholar]
  36. Stetler-Stevenson W. G., Aznavoorian S., Liotta L. A. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol. 1993;9:541–573. doi: 10.1146/annurev.cb.09.110193.002545. [DOI] [PubMed] [Google Scholar]
  37. Stolow M. A., Bauzon D. D., Li J., Sedgwick T., Liang V. C., Sang Q. A., Shi Y. B. Identification and characterization of a novel collagenase in Xenopus laevis: possible roles during frog development. Mol Biol Cell. 1996 Oct;7(10):1471–1483. doi: 10.1091/mbc.7.10.1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Talhouk R. S., Bissell M. J., Werb Z. Coordinated expression of extracellular matrix-degrading proteinases and their inhibitors regulates mammary epithelial function during involution. J Cell Biol. 1992 Sep;118(5):1271–1282. doi: 10.1083/jcb.118.5.1271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tryggvason K., Höyhtyä M., Salo T. Proteolytic degradation of extracellular matrix in tumor invasion. Biochim Biophys Acta. 1987 Nov 25;907(3):191–217. doi: 10.1016/0304-419x(87)90006-0. [DOI] [PubMed] [Google Scholar]
  40. Tsukiyama T., Becker P. B., Wu C. ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature. 1994 Feb 10;367(6463):525–532. doi: 10.1038/367525a0. [DOI] [PubMed] [Google Scholar]
  41. Tsukiyama T., Wu C. Purification and properties of an ATP-dependent nucleosome remodeling factor. Cell. 1995 Dec 15;83(6):1011–1020. doi: 10.1016/0092-8674(95)90216-3. [DOI] [PubMed] [Google Scholar]
  42. Tsukiyama T., Wu C. Purification of GAGA factor of Drosophila and its role in nucleosome disruption. Methods Enzymol. 1996;274:291–299. doi: 10.1016/s0076-6879(96)74025-9. [DOI] [PubMed] [Google Scholar]
  43. Van Wart H. E., Birkedal-Hansen H. The cysteine switch: a principle of regulation of metalloproteinase activity with potential applicability to the entire matrix metalloproteinase gene family. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5578–5582. doi: 10.1073/pnas.87.14.5578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wang Z., Brown D. D. Thyroid hormone-induced gene expression program for amphibian tail resorption. J Biol Chem. 1993 Aug 5;268(22):16270–16278. [PubMed] [Google Scholar]
  45. Woessner J. F., Jr Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991 May;5(8):2145–2154. [PubMed] [Google Scholar]
  46. Zawel L., Reinberg D. Initiation of transcription by RNA polymerase II: a multi-step process. Prog Nucleic Acid Res Mol Biol. 1993;44:67–108. doi: 10.1016/s0079-6603(08)60217-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES