Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1990 Mar;9(3):833–840. doi: 10.1002/j.1460-2075.1990.tb08180.x

Tissue-specific control elements of the Thy-1 gene.

M Vidal 1, R Morris 1, F Grosveld 1, E Spanopoulou 1
PMCID: PMC551743  PMID: 1968831

Abstract

We have exploited the structural homology, but different patterns of expression of the murine and human Thy-1 genes to map a number of tissue-specific enhancer elements in the genes. All of these are located downstream from the site of transcriptional initiation. The human gene contains separate elements which direct expression to the kidney or spleen epithelium. The murine gene lacks these elements but instead contains a thymocyte specific enhancer in the third intron. Developmentally-regulated expression in nerve cells is directed (at least in part) by an atypical element in the first intron. The latter is active on heterologous promoters, but is position and distance dependent.

Full text

PDF
833

Images in this article

834Fig. 2.
on p.834
836Fig. 4.
on p.836
836Fig. 5.
on p.836
837Fig. 6.
on p.837

Selected References

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

  1. Aronow B., Lattier D., Silbiger R., Dusing M., Hutton J., Jones G., Stock J., McNeish J., Potter S., Witte D. Evidence for a complex regulatory array in the first intron of the human adenosine deaminase gene. Genes Dev. 1989 Sep;3(9):1384–1400. doi: 10.1101/gad.3.9.1384. [DOI] [PubMed] [Google Scholar]
  2. Atchison M. L. Enhancers: mechanisms of action and cell specificity. Annu Rev Cell Biol. 1988;4:127–153. doi: 10.1146/annurev.cb.04.110188.001015. [DOI] [PubMed] [Google Scholar]
  3. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  4. Basler K., Siegrist P., Hafen E. The spatial and temporal expression pattern of sevenless is exclusively controlled by gene-internal elements. EMBO J. 1989 Aug;8(8):2381–2386. doi: 10.1002/j.1460-2075.1989.tb08367.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  6. Benvenisty N., Nechushtan H., Cohen H., Reshef L. Separate cis-regulatory elements confer expression of phosphoenolpyruvate carboxykinase (GTP) gene in different cell lines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1118–1122. doi: 10.1073/pnas.86.4.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bienz M., Saari G., Tremml G., Müller J., Züst B., Lawrence P. A. Differential regulation of Ultrabithorax in two germ layers of Drosophila. Cell. 1988 May 20;53(4):567–576. doi: 10.1016/0092-8674(88)90573-9. [DOI] [PubMed] [Google Scholar]
  8. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  9. Bornstein P., McKay J., Liska D. J., Apone S., Devarayalu S. Interactions between the promoter and first intron are involved in transcriptional control of alpha 1(I) collagen gene expression. Mol Cell Biol. 1988 Nov;8(11):4851–4857. doi: 10.1128/mcb.8.11.4851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brinster R. L., Allen J. M., Behringer R. R., Gelinas R. E., Palmiter R. D. Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci U S A. 1988 Feb;85(3):836–840. doi: 10.1073/pnas.85.3.836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chen S., Botteri F., van der Putten H., Landel C. P., Evans G. A. A lymphoproliferative abnormality associated with inappropriate expression of the Thy-1 antigen in transgenic mice. Cell. 1987 Oct 9;51(1):7–19. doi: 10.1016/0092-8674(87)90005-5. [DOI] [PubMed] [Google Scholar]
  12. Chung S., Perry R. P. Importance of introns for expression of mouse ribosomal protein gene rpL32. Mol Cell Biol. 1989 May;9(5):2075–2082. doi: 10.1128/mcb.9.5.2075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Clevers H., Lonberg N., Dunlap S., Lacy E., Terhorst C. An enhancer located in a CpG-island 3' to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter. EMBO J. 1989 Sep;8(9):2527–2535. doi: 10.1002/j.1460-2075.1989.tb08390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cohen F. E., Novotný J., Sternberg M. J., Campbell D. G., Williams A. F. Analysis of structural similarities between brain Thy-1 antigen and immunoglobulin domains. Evidence for an evolutionary relationship and a hypothesis for its functional significance. Biochem J. 1981 Apr 1;195(1):31–40. doi: 10.1042/bj1950031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Colantuoni V., Pirozzi A., Blance C., Cortese R. Negative control of liver-specific gene expression: cloned human retinol-binding protein gene is repressed in HeLa cells. EMBO J. 1987 Mar;6(3):631–636. doi: 10.1002/j.1460-2075.1987.tb04801.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Collis P., Antoniou M., Grosveld F. Definition of the minimal requirements within the human beta-globin gene and the dominant control region for high level expression. EMBO J. 1990 Jan;9(1):233–240. doi: 10.1002/j.1460-2075.1990.tb08100.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cooper E. L., Mansour M. H. Distribution of Thy-1 in invertebrates and ectothermic vertebrates. Immunol Ser. 1989;45:197–219. [PubMed] [Google Scholar]
  18. Danciger E., Mettling C., Vidal M., Morris R., Margolis F. Olfactory marker protein gene: its structure and olfactory neuron-specific expression in transgenic mice. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8565–8569. doi: 10.1073/pnas.86.21.8565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dodd J., Jessell T. M. Axon guidance and the patterning of neuronal projections in vertebrates. Science. 1988 Nov 4;242(4879):692–699. doi: 10.1126/science.3055291. [DOI] [PubMed] [Google Scholar]
  20. Foon K. A., Neubauer R. H., Wikstrand C. J., Schroff R. W., Rabin H., Seeger R. C. A monoclonal antibody recognizing human Thy-1: distribution on human and non-human primate haematopoietic cells. J Immunogenet. 1984 Jun-Aug;11(3-4):233–243. doi: 10.1111/j.1744-313x.1984.tb01059.x. [DOI] [PubMed] [Google Scholar]
  21. Garabedian M. J., Hung M. C., Wensink P. C. Independent control elements that determine yolk protein gene expression in alternative Drosophila tissues. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1396–1400. doi: 10.1073/pnas.82.5.1396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Geyer P. K., Corces V. G. Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes Dev. 1987 Nov;1(9):996–1004. doi: 10.1101/gad.1.9.996. [DOI] [PubMed] [Google Scholar]
  25. Giguére V., Isobe K., Grosveld F. Structure of the murine Thy-1 gene. EMBO J. 1985 Aug;4(8):2017–2024. doi: 10.1002/j.1460-2075.1985.tb03886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Gordon J. W., Chesa P. G., Nishimura H., Rettig W. J., Maccari J. E., Endo T., Seravalli E., Seki T., Silver J. Regulation of Thy-1 gene expression in transgenic mice. Cell. 1987 Jul 31;50(3):445–452. doi: 10.1016/0092-8674(87)90498-3. [DOI] [PubMed] [Google Scholar]
  27. Gottesdiener K. M., Karpinski B. A., Lindsten T., Strominger J. L., Jones N. H., Thompson C. B., Leiden J. M. Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation. Mol Cell Biol. 1988 Sep;8(9):3809–3819. doi: 10.1128/mcb.8.9.3809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Greaves D. R., Wilson F. D., Lang G., Kioussis D. Human CD2 3'-flanking sequences confer high-level, T cell-specific, position-independent gene expression in transgenic mice. Cell. 1989 Mar 24;56(6):979–986. doi: 10.1016/0092-8674(89)90631-4. [DOI] [PubMed] [Google Scholar]
  29. Grosveld F., Kollias G. Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities. Cell. 1988 Sep 23;54(7):920–920. doi: 10.1016/0092-8674(88)90105-5. [DOI] [PubMed] [Google Scholar]
  30. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  31. Harrelson A. L., Goodman C. S. Growth cone guidance in insects: fasciclin II is a member of the immunoglobulin superfamily. Science. 1988 Nov 4;242(4879):700–708. doi: 10.1126/science.3187519. [DOI] [PubMed] [Google Scholar]
  32. Hiromi Y., Kuroiwa A., Gehring W. J. Control elements of the Drosophila segmentation gene fushi tarazu. Cell. 1985 Dec;43(3 Pt 2):603–613. doi: 10.1016/0092-8674(85)90232-6. [DOI] [PubMed] [Google Scholar]
  33. Horton W., Miyashita T., Kohno K., Hassell J. R., Yamada Y. Identification of a phenotype-specific enhancer in the first intron of the rat collagen II gene. Proc Natl Acad Sci U S A. 1987 Dec;84(24):8864–8868. doi: 10.1073/pnas.84.24.8864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ingraham H. A., Evans G. A. Characterization of two atypical promoters and alternate mRNA processing in the mouse Thy-1.2 glycoprotein gene. Mol Cell Biol. 1986 Aug;6(8):2923–2931. doi: 10.1128/mcb.6.8.2923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Johnson W. A., McCormick C. A., Bray S. J., Hirsh J. A neuron-specific enhancer of the Drosophila dopa decarboxylase gene. Genes Dev. 1989 May;3(5):676–686. doi: 10.1101/gad.3.5.676. [DOI] [PubMed] [Google Scholar]
  36. Julien J. P., Tretjakoff I., Beaudet L., Peterson A. Expression and assembly of a human neurofilament protein in transgenic mice provide a novel neuronal marking system. Genes Dev. 1987 Dec;1(10):1085–1095. doi: 10.1101/gad.1.10.1085. [DOI] [PubMed] [Google Scholar]
  37. Kimura A., Israël A., Le Bail O., Kourilsky P. Detailed analysis of the mouse H-2Kb promoter: enhancer-like sequences and their role in the regulation of class I gene expression. Cell. 1986 Jan 31;44(2):261–272. doi: 10.1016/0092-8674(86)90760-9. [DOI] [PubMed] [Google Scholar]
  38. Kollias G., Evans D. J., Ritter M., Beech J., Morris R., Grosveld F. Ectopic expression of Thy-1 in the kidneys of transgenic mice induces functional and proliferative abnormalities. Cell. 1987 Oct 9;51(1):21–31. doi: 10.1016/0092-8674(87)90006-7. [DOI] [PubMed] [Google Scholar]
  39. Kollias G., Spanopoulou E., Grosveld F., Ritter M., Beech J., Morris R. Differential regulation of a Thy-1 gene in transgenic mice. Proc Natl Acad Sci U S A. 1987 Mar;84(6):1492–1496. doi: 10.1073/pnas.84.6.1492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Low M. G., Kincade P. W. Phosphatidylinositol is the membrane-anchoring domain of the Thy-1 glycoprotein. Nature. 1985 Nov 7;318(6041):62–64. doi: 10.1038/318062a0. [DOI] [PubMed] [Google Scholar]
  42. Luskey K. L. Conservation of promoter sequence but not complex intron splicing pattern in human and hamster genes for 3-hydroxy-3-methylglutaryl coenzyme A reductase. Mol Cell Biol. 1987 May;7(5):1881–1893. doi: 10.1128/mcb.7.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. McKenzie J. L., Fabre J. W. Human thy-1: unusual localization and possible functional significance in lymphoid tissues. J Immunol. 1981 Mar;126(3):843–850. [PubMed] [Google Scholar]
  44. Mellor J., Dobson M. J., Kingsman A. J., Kingsman S. M. A transcriptional activator is located in the coding region of the yeast PGK gene. Nucleic Acids Res. 1987 Aug 11;15(15):6243–6259. doi: 10.1093/nar/15.15.6243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Morris R., Grosveld F. Expression of Thy-1 in the nervous system of the rat and mouse. Immunol Ser. 1989;45:121–148. [PubMed] [Google Scholar]
  46. Morris R. Thy-1 in developing nervous tissue. Dev Neurosci. 1985;7(3):133–160. doi: 10.1159/000112283. [DOI] [PubMed] [Google Scholar]
  47. Nepveu A., Marcu K. B. Intragenic pausing and anti-sense transcription within the murine c-myc locus. EMBO J. 1986 Nov;5(11):2859–2865. doi: 10.1002/j.1460-2075.1986.tb04580.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. REIF A. E., ALLEN J. M. SPECIFICITY OF ISOANTISERA AGAINST LEUKAEMIC AND THYMIC LYMPHOCYTES. Nature. 1963 Dec 28;200:1332–1333. doi: 10.1038/2001332b0. [DOI] [PubMed] [Google Scholar]
  49. Ritter M. A., Sauvage C. A., Cotmore S. F. The human thymus microenvironment: in vivo identification of thymic nurse cells and other antigenically-distinct subpopulations of epithelial cells. Immunology. 1981 Nov;44(3):439–446. [PMC free article] [PubMed] [Google Scholar]
  50. Rossi P., de Crombrugghe B. Identification of a cell-specific transcriptional enhancer in the first intron of the mouse alpha 2 (type I) collagen gene. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5590–5594. doi: 10.1073/pnas.84.16.5590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Sastry K. N., Seedorf U., Karathanasis S. K. Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types. Mol Cell Biol. 1988 Feb;8(2):605–614. doi: 10.1128/mcb.8.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Seki T., Spurr N., Obata F., Goyert S., Goodfellow P., Silver J. The human Thy-1 gene: structure and chromosomal location. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6657–6661. doi: 10.1073/pnas.82.19.6657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Spanopoulou E., Early A., Elliott J., Crispe N., Ladyman H., Ritter M., Watt S., Grosveld F., Kioussis D. Complex lymphoid and epithelial thymic tumours in Thy1-myc transgenic mice. Nature. 1989 Nov 9;342(6246):185–189. doi: 10.1038/342185a0. [DOI] [PubMed] [Google Scholar]
  54. Spanopoulou E., Giguere V., Grosveld F. Transcriptional unit of the murine Thy-1 gene: different distribution of transcription initiation sites in brain. Mol Cell Biol. 1988 Sep;8(9):3847–3856. doi: 10.1128/mcb.8.9.3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sternberg E. A., Spizz G., Perry W. M., Vizard D., Weil T., Olson E. N. Identification of upstream and intragenic regulatory elements that confer cell-type-restricted and differentiation-specific expression on the muscle creatine kinase gene. Mol Cell Biol. 1988 Jul;8(7):2896–2909. doi: 10.1128/mcb.8.7.2896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Tse A. G., Barclay A. N., Watts A., Williams A. F. A glycophospholipid tail at the carboxyl terminus of the Thy-1 glycoprotein of neurons and thymocytes. Science. 1985 Nov 29;230(4729):1003–1008. doi: 10.1126/science.2865810. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. Williams A. F., Gagnon J. Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin. Science. 1982 May 14;216(4547):696–703. doi: 10.1126/science.6177036. [DOI] [PubMed] [Google Scholar]
  59. Winoto A., Baltimore D. A novel, inducible and T cell-specific enhancer located at the 3' end of the T cell receptor alpha locus. EMBO J. 1989 Mar;8(3):729–733. doi: 10.1002/j.1460-2075.1989.tb03432.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Yutzey K. E., Kline R. L., Konieczny S. F. An internal regulatory element controls troponin I gene expression. Mol Cell Biol. 1989 Apr;9(4):1397–1405. doi: 10.1128/mcb.9.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES