Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Sep 1;88(17):7859–7863. doi: 10.1073/pnas.88.17.7859

Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene.

M I Cybulsky 1, J W Fries 1, A J Williams 1, P Sultan 1, R Eddy 1, M Byers 1, T Shows 1, M A Gimbrone Jr 1, T Collins 1
PMCID: PMC52403  PMID: 1715583

Abstract

Vascular cell adhesion molecule 1 (VCAM-1) is a cell surface glycoprotein adhesive for certain blood leukocytes and tumor cells, which is expressed by activated endothelium in a variety of pathologic conditions including atherosclerosis. Genomic clones encoding the VCAM1 gene were isolated and the organization of the gene was determined. The gene, which is present in a single copy in the human genome, contains 9 exons spanning approximately 25 kilobases of DNA. Exons 2-8 contain C2 or H-type immunoglobulin domains. At least two different VCAM-1 precursors can be generated from the human gene as a result of alternative mRNA splicing events, which include or exclude exon 5. A consensus TATAA element is located upstream of the transcriptional start site. The VCAM1 promoter contains consensus binding sites for NF-kappa B, the GATA family of transcription factors, as well as an AP1 site. The VCAM1 gene was assigned to the 1p31-32 region of chromosome 1 based on the analysis of human-mouse hybrid cell lines and in situ hybridization. Structural analysis of the human VCAM1 gene provides the basis for alternative mRNA splicing and an initial approach to elucidating the regulation of VCAM-1 expression.

Full text

PDF
7862

Images in this article

7862Image
on p.7862
7862Image
on p.7862
7862Image
on p.7862

Selected References

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

  1. Balaban G. B., Herlyn M., Clark W. H., Jr, Nowell P. C. Karyotypic evolution in human malignant melanoma. Cancer Genet Cytogenet. 1986 Jan 1;19(1-2):113–122. doi: 10.1016/0165-4608(86)90378-x. [DOI] [PubMed] [Google Scholar]
  2. Birnstiel M. L., Busslinger M., Strub K. Transcription termination and 3' processing: the end is in site! Cell. 1985 Jun;41(2):349–359. doi: 10.1016/s0092-8674(85)80007-6. [DOI] [PubMed] [Google Scholar]
  3. Bochner B. S., Luscinskas F. W., Gimbrone M. A., Jr, Newman W., Sterbinsky S. A., Derse-Anthony C. P., Klunk D., Schleimer R. P. Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules. J Exp Med. 1991 Jun 1;173(6):1553–1557. doi: 10.1084/jem.173.6.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bonthron D. T., Morton C. C., Orkin S. H., Collins T. Platelet-derived growth factor A chain: gene structure, chromosomal location, and basis for alternative mRNA splicing. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1492–1496. doi: 10.1073/pnas.85.5.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  6. Briscoe D. M., Schoen F. J., Rice G. E., Bevilacqua M. P., Ganz P., Pober J. S. Induced expression of endothelial-leukocyte adhesion molecules in human cardiac allografts. Transplantation. 1991 Feb;51(2):537–539. [PubMed] [Google Scholar]
  7. Brown M. H., Gorman P. A., Sewell W. A., Spurr N. K., Sheer D., Crumpton M. J. The gene coding for the human T-lymphocyte CD2 antigen is located on chromosome 1p. Hum Genet. 1987 Jun;76(2):191–195. doi: 10.1007/BF00284920. [DOI] [PubMed] [Google Scholar]
  8. Chen Q., Cheng J. T., Tasi L. H., Schneider N., Buchanan G., Carroll A., Crist W., Ozanne B., Siciliano M. J., Baer R. The tal gene undergoes chromosome translocation in T cell leukemia and potentially encodes a helix-loop-helix protein. EMBO J. 1990 Feb;9(2):415–424. doi: 10.1002/j.1460-2075.1990.tb08126.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Collins T., Pober J. S., Gimbrone M. A., Jr, Hammacher A., Betsholtz C., Westermark B., Heldin C. H. Cultured human endothelial cells express platelet-derived growth factor A chain. Am J Pathol. 1987 Jan;126(1):7–12. [PMC free article] [PubMed] [Google Scholar]
  10. Collins T., Williams A., Johnston G. I., Kim J., Eddy R., Shows T., Gimbrone M. A., Jr, Bevilacqua M. P. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem. 1991 Feb 5;266(4):2466–2473. [PubMed] [Google Scholar]
  11. Cybulsky M. I., Fries J. W., Williams A. J., Sultan P., Davis V. M., Gimbrone M. A., Jr, Collins T. Alternative splicing of human VCAM-1 in activated vascular endothelium. Am J Pathol. 1991 Apr;138(4):815–820. [PMC free article] [PubMed] [Google Scholar]
  12. Cybulsky M. I., Gimbrone M. A., Jr Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science. 1991 Feb 15;251(4995):788–791. doi: 10.1126/science.1990440. [DOI] [PubMed] [Google Scholar]
  13. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  14. Fan Y. S., Davis L. M., Shows T. B. Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6223–6227. doi: 10.1073/pnas.87.16.6223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Finger L. R., Kagan J., Christopher G., Kurtzberg J., Hershfield M. S., Nowell P. C., Croce C. M. Involvement of the TCL5 gene on human chromosome 1 in T-cell leukemia and melanoma. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5039–5043. doi: 10.1073/pnas.86.13.5039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gilbert F., Balaban G., Moorhead P., Bianchi D., Schlesinger H. Abnormalities of chromosome 1p in human neuroblastoma tumors and cell lines. Cancer Genet Cytogenet. 1982 Sep;7(1):33–42. doi: 10.1016/0165-4608(82)90105-4. [DOI] [PubMed] [Google Scholar]
  18. Goldstein J. L., Brown M. S. Regulation of the mevalonate pathway. Nature. 1990 Feb 1;343(6257):425–430. doi: 10.1038/343425a0. [DOI] [PubMed] [Google Scholar]
  19. Hession C., Tizard R., Vassallo C., Schiffer S. B., Goff D., Moy P., Chi-Rosso G., Luhowskyj S., Lobb R., Osborn L. Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). J Biol Chem. 1991 Apr 15;266(11):6682–6685. [PubMed] [Google Scholar]
  20. Lee W., Haslinger A., Karin M., Tjian R. Activation of transcription by two factors that bind promoter and enhancer sequences of the human metallothionein gene and SV40. Nature. 1987 Jan 22;325(6102):368–372. doi: 10.1038/325368a0. [DOI] [PubMed] [Google Scholar]
  21. Lenardo M. J., Baltimore D. NF-kappa B: a pleiotropic mediator of inducible and tissue-specific gene control. Cell. 1989 Jul 28;58(2):227–229. doi: 10.1016/0092-8674(89)90833-7. [DOI] [PubMed] [Google Scholar]
  22. Marth J. D., Disteche C., Pravtcheva D., Ruddle F., Krebs E. G., Perlmutter R. M. Localization of a lymphocyte-specific protein tyrosine kinase gene (lck) at a site of frequent chromosomal abnormalities in human lymphomas. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7400–7404. doi: 10.1073/pnas.83.19.7400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Osborn L., Hession C., Tizard R., Vassallo C., Luhowskyj S., Chi-Rosso G., Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. doi: 10.1016/0092-8674(89)90775-7. [DOI] [PubMed] [Google Scholar]
  25. Pober J. S., Cotran R. S. Cytokines and endothelial cell biology. Physiol Rev. 1990 Apr;70(2):427–451. doi: 10.1152/physrev.1990.70.2.427. [DOI] [PubMed] [Google Scholar]
  26. Rice G. E., Bevilacqua M. P. An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. Science. 1989 Dec 8;246(4935):1303–1306. doi: 10.1126/science.2588007. [DOI] [PubMed] [Google Scholar]
  27. Rice G. E., Munro J. M., Bevilacqua M. P. Inducible cell adhesion molecule 110 (INCAM-110) is an endothelial receptor for lymphocytes. A CD11/CD18-independent adhesion mechanism. J Exp Med. 1990 Apr 1;171(4):1369–1374. doi: 10.1084/jem.171.4.1369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rice G. E., Munro J. M., Corless C., Bevilacqua M. P. Vascular and nonvascular expression of INCAM-110. A target for mononuclear leukocyte adhesion in normal and inflamed human tissues. Am J Pathol. 1991 Feb;138(2):385–393. [PMC free article] [PubMed] [Google Scholar]
  29. Sewell W. A., Palmer R. W., Spurr N. K., Sheer D., Brown M. H., Bell Y., Crumpton M. J. The human LFA-3 gene is located at the same chromosome band as the gene for its receptor CD2. Immunogenetics. 1988;28(4):278–282. doi: 10.1007/BF00345506. [DOI] [PubMed] [Google Scholar]
  30. Sharp P. A. Speculations on RNA splicing. Cell. 1981 Mar;23(3):643–646. doi: 10.1016/0092-8674(81)90425-6. [DOI] [PubMed] [Google Scholar]
  31. Shows T. B., Sakaguchi A. Y., Naylor S. L. Mapping the human genome, cloned genes, DNA polymorphisms, and inherited disease. Adv Hum Genet. 1982;12:341–452. doi: 10.1007/978-1-4615-8315-8_5. [DOI] [PubMed] [Google Scholar]
  32. Smith M. W. Structure of vertebrate genes: a statistical analysis implicating selection. J Mol Evol. 1988;27(1):45–55. doi: 10.1007/BF02099729. [DOI] [PubMed] [Google Scholar]
  33. Taichman D. B., Cybulsky M. I., Djaffar I., Longenecker B. M., Teixidó J., Rice G. E., Aruffo A., Bevilacqua M. P. Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. Cell Regul. 1991 May;2(5):347–355. doi: 10.1091/mbc.2.5.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
  35. Williams A. F., Barclay A. N. The immunoglobulin superfamily--domains for cell surface recognition. Annu Rev Immunol. 1988;6:381–405. doi: 10.1146/annurev.iy.06.040188.002121. [DOI] [PubMed] [Google Scholar]
  36. Wilson D. B., Dorfman D. M., Orkin S. H. A nonerythroid GATA-binding protein is required for function of the human preproendothelin-1 promoter in endothelial cells. Mol Cell Biol. 1990 Sep;10(9):4854–4862. doi: 10.1128/mcb.10.9.4854. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES