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. 1989 Mar;8(3):729–733. doi: 10.1002/j.1460-2075.1989.tb03432.x

A novel, inducible and T cell-specific enhancer located at the 3' end of the T cell receptor alpha locus.

A Winoto 1, D Baltimore 1
PMCID: PMC400868  PMID: 2524381

Abstract

A novel, powerful and T-cell-specific enhancer element has been identified at 3 kb 3' of the mouse T cell receptor (TCR) C alpha (constant) gene. A previous report of an intragenic enhancer could not be confirmed. The unique organization of the TCR alpha locus and transcriptional data of the alpha promoter suggest that this enhancer can act over 69 kb. This feature of the alpha enhancer may lead to deregulation of c-myc and other oncogenes translocated to this locus in many T cell leukemias, resulting in T cell neoplasia. The enhancer was localized to 230 bp of DNA and has been found to be inducible in an immature T lymphoid cell line. Deletions localizing critical regions and T-cell-specific binding proteins of this enhancer are described.

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Selected References

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  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. Berg L. J., Fazekas de St Groth B., Ivars F., Goodnow C. C., Gilfillan S., Garchon H. J., Davis M. M. Expression of T-cell receptor alpha-chain genes in transgenic mice. Mol Cell Biol. 1988 Dec;8(12):5459–5469. doi: 10.1128/mcb.8.12.5459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  4. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  5. Erikson J., Finger L., Sun L., ar-Rushdi A., Nishikura K., Minowada J., Finan J., Emanuel B. S., Nowell P. C., Croce C. M. Deregulation of c-myc by translocation of the alpha-locus of the T-cell receptor in T-cell leukemias. Science. 1986 May 16;232(4752):884–886. doi: 10.1126/science.3486470. [DOI] [PubMed] [Google Scholar]
  6. Georgopoulos K., van den Elsen P., Bier E., Maxam A., Terhorst C. A T cell-specific enhancer is located in a DNase I-hypersensitive area at the 3' end of the CD3-delta gene. EMBO J. 1988 Aug;7(8):2401–2407. doi: 10.1002/j.1460-2075.1988.tb03085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Jones N. C., Rigby P. W., Ziff E. B. Trans-acting protein factors and the regulation of eukaryotic transcription: lessons from studies on DNA tumor viruses. Genes Dev. 1988 Mar;2(3):267–281. doi: 10.1101/gad.2.3.267. [DOI] [PubMed] [Google Scholar]
  10. Krimpenfort P., de Jong R., Uematsu Y., Dembic Z., Ryser S., von Boehmer H., Steinmetz M., Berns A. Transcription of T cell receptor beta-chain genes is controlled by a downstream regulatory element. EMBO J. 1988 Mar;7(3):745–750. doi: 10.1002/j.1460-2075.1988.tb02871.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kronenberg M., Siu G., Hood L. E., Shastri N. The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Annu Rev Immunol. 1986;4:529–591. doi: 10.1146/annurev.iy.04.040186.002525. [DOI] [PubMed] [Google Scholar]
  12. Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
  13. Luria S., Gross G., Horowitz M., Givol D. Promoter and enhancer elements in the rearranged alpha chain gene of the human T cell receptor. EMBO J. 1987 Nov;6(11):3307–3312. doi: 10.1002/j.1460-2075.1987.tb02650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Maniatis T., Goodbourn S., Fischer J. A. Regulation of inducible and tissue-specific gene expression. Science. 1987 Jun 5;236(4806):1237–1245. doi: 10.1126/science.3296191. [DOI] [PubMed] [Google Scholar]
  15. McDougall S., Peterson C. L., Calame K. A transcriptional enhancer 3' of C beta 2 in the T cell receptor beta locus. Science. 1988 Jul 8;241(4862):205–208. doi: 10.1126/science.2968651. [DOI] [PubMed] [Google Scholar]
  16. Paige C. J., Kincade P. W., Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978 Aug;121(2):641–647. [PubMed] [Google Scholar]
  17. Pierce J. W., Lenardo M., Baltimore D. Oligonucleotide that binds nuclear factor NF-kappa B acts as a lymphoid-specific and inducible enhancer element. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1482–1486. doi: 10.1073/pnas.85.5.1482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Raulet D. H., Garman R. D., Saito H., Tonegawa S. Developmental regulation of T-cell receptor gene expression. Nature. 1985 Mar 7;314(6006):103–107. doi: 10.1038/314103a0. [DOI] [PubMed] [Google Scholar]
  20. Sakaguchi N., Kishimoto T., Kikutani H., Watanabe T., Yoshida N., Shimizu A., Yamawaki-Kataoka Y., Honjo T., Yamamura Y. Induction and regulation of immunoglobulin expression in a murine pre-B cell line, 70Z/3. I. Cell cycle-associated induction of sIgM expression and kappa-chain synthesis in 70Z/3 cells by LPS stimulation. J Immunol. 1980 Dec;125(6):2654–2659. [PubMed] [Google Scholar]
  21. Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
  22. Shackelford D. A., Smith A. V., Trowbridge I. S. Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor. J Immunol. 1987 Jan 15;138(2):613–619. [PubMed] [Google Scholar]
  23. Snodgrass H. R., Dembić Z., Steinmetz M., von Boehmer H. Expression of T-cell antigen receptor genes during fetal development in the thymus. Nature. 1985 May 16;315(6016):232–233. doi: 10.1038/315232a0. [DOI] [PubMed] [Google Scholar]
  24. Toyonaga B., Mak T. W. Genes of the T-cell antigen receptor in normal and malignant T cells. Annu Rev Immunol. 1987;5:585–620. doi: 10.1146/annurev.iy.05.040187.003101. [DOI] [PubMed] [Google Scholar]
  25. Wingender E. Compilation of transcription regulating proteins. Nucleic Acids Res. 1988 Mar 25;16(5):1879–1902. doi: 10.1093/nar/16.5.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yoshikai Y., Clark S. P., Taylor S., Sohn U., Wilson B. I., Minden M. D., Mak T. W. Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor alpha-chain. 1985 Aug 29-Sep 4Nature. 316(6031):837–840. doi: 10.1038/316837a0. [DOI] [PubMed] [Google Scholar]

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