Skip to main content
SpringerLink
Log in

Control of transcription at the murine Aα locus

  • MHC Class II Genes and Molecules, Symposium (Part II)
  • Published:
Immunologic Research Aims and scope Submit manuscript

Conclusion

Our studies to date have implicated several separate DNA elements in Aα gene transcription in B cells: the conserved X-Y region and two related elements further upstream than the X-Y region. Important transcription elements for monocyte/macrophage lineage cells have tended to map much closer to the conserved region than those of B cells [45, 46]; however, we have not yet rigorously tested the control of Aα sequences in macrophages. We conclude from our data on the X box that each murine X box is bound by a different set of proteins, though the major complex generated with an Eα probe may have reflected binding by the same protein as the main Eβ complex [47]. Cloned cDNAs encoding Aα X box-X-Y interspace binding proteins [48] will further the analysis of transcription biochemistry for Aα. We also conclude that DNA sequences upstream from Aα are important in B-cell-specific cis-activation of transcription, that this function will at least in part be mediated by a DNA-binding protein that binds to two sites upstream from X and Y in Aα and that these sites will be essential for IL-4-induced increases in transcription. Tests of these observations will hopefully lead to a greater degree of understanding of the control of class II transcription, as well as of its failure in class II-deficient bare lymphocyte syndrome SCID patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Janeway, C.A., Jr.; Bottomly, K.; Babich, J.; Conrad, P.; Conzen, S.; Jones, B.; Kaye, J.; Katz, M.; McVay, L.; Murphy, D.; Tite, J.: Quantitative variation in Ia antigen expression plays a central role in immune regulation. Immunol. Today5: 99–104 (1984).

    Article  CAS  Google Scholar 

  2. Matis, L.A.; Glimcher, L.H.; Paul, W.E.; Schwartz, R.H.: Magnitude of response of histocompatibility-restricted T cell clones ios a function of the product of the concentration of antigen and Ia molecules. Proc. natn. Acad. Sci. USA80: 6019–6023 (1983).

    Article  CAS  Google Scholar 

  3. Noelle, R.; Krammer, P.H.; Ohara, J.; Uhr, J.W.; Vitetta, E.S.: Increased expression of Ia antigens on resting B cells: additional role for B-cell growth factor. Proc. natn. Acad. Sci. USA81: 6149–6153 (1984).

    Article  CAS  Google Scholar 

  4. Collins, T.; Pober, J.S.; Strominger, J.L.: Physiologic regulation of class II MHC gene expression; in Solheim, Moller, Ferrone, HLA class II antigens. p. 14 (Springer, Berlin 1987).

    Google Scholar 

  5. King, D.P.; Jones, P.P. Induction of Ia and H-2 antigens on a marophage cell line by immune interferon. J. Immun.131: 315–318 (1983).

    PubMed  CAS  Google Scholar 

  6. Mond, J.J.; Seghal, E.; Kung, J.; Finkelman, F.D.: Increased expression of I-region-associated antigen (Ia) on B cells after crosslinking of surface immunoglobulin. J. Immun.127: 881–888 (1981).

    PubMed  CAS  Google Scholar 

  7. Goroff, D.K.; Stall, A.; Mond, J.J.; Finkelman, F.D.: In vitro and in vivo B lymphocyte activity properties of monoclonal anti-delta antibodies. J. Immun.136: 2382–2392 (1986).

    PubMed  CAS  Google Scholar 

  8. Polla, B.S.; Poljak, A.; Geier, S.G.; Nathenson, S.G.; Ohara, J.; Paul, W.E.; Glimcher, L.H.: Three distinct signals can induce class II gene expression in a murine pre-B-cell line. Proc. natn. Acad. Sci. USA83: 4878–4882 (1986).

    Article  CAS  Google Scholar 

  9. Polla, B.S.; Ohara, J.; Paul, W.E.; Nabavi, N.; Myer, A.; Liou, H.-C.; Shen, F.-W.; Gillis, S.; Bonventre, J.V.; Glimcher, L.H.: Differential induction of class II gene expression in murine pre-B-cell lines by B-cell stimulatory factor-1 and by antibodies to B-cell surface antigens. J. mol. Cell. Immunol.3: 363–373 (1988).

    PubMed  CAS  Google Scholar 

  10. Dennis, G.J.; Mizuguchi, J.; McMillan, V.; Finkelman, F.D.; Ohara, J.; Mond, J.J.: Comparison of the calcium-requirement for the induction and maintenance of B cell class II molecule expression and for B cell proliferation stimulated mitogens and purified growth factors. J. Immun.138: 4307–4312 (1987).

    PubMed  CAS  Google Scholar 

  11. McMillan, V.M.; Dennis, G.J.; Glimcher, L.H.; Finkelman, F.D.; Mond, J.J.: Corticosteroid induction of Ig+Ia− B cells in vitro is mediated via interaction with the glucocorticoid cytoplasmic receptor. J. Immun.140: 2549–2555 (1988).

    PubMed  CAS  Google Scholar 

  12. Noelle, R.; Kuziel, W.A.; Maliszewski, C.R.; McAdams, E.; Vitetta, E.S.; Tucker, P.W.: Regulation of the expression of multiple class II genes in murine B cells by B cell stimulatory factor-1 (BSF-1). J. Immun.137: 1718–1723 (1986).

    PubMed  CAS  Google Scholar 

  13. Polla, B.S.; Poljak, A.; Ohara, J.; Paul, W.E.; Glimcher, L.H.: Regulation of class II gene expression: analysis in B-cell stimulatory factor-I inducible murine pre-B cell lines. J. Immun.137: 3332–3337 (1986).

    PubMed  CAS  Google Scholar 

  14. Blanar, M.A.; Boettger, E.G.; Flavell, R.A.: Transcriptional activation of HLA-DRα by interferon-γ requires a transacting protein. Proc. natn. Acad. Sci. USA85: 4672–4676 (1988).

    Article  CAS  Google Scholar 

  15. Calman, A.F.; Peterlin, B.M.: Mutant human B cell lines deficient in class II major histocompatibility complex transcription. J. Immun.139: 2489–2495 (1987).

    PubMed  CAS  Google Scholar 

  16. Boothby, M.; Gravallese, E.; Liou, H.-C.; Glimcher, L.H.: A DNA-binding protein regulated by IL-4 and by differentiation in B cells. Science242: 1559–1562 (1988).

    Article  PubMed  CAS  Google Scholar 

  17. Maniatis, T.; Goodbourn, S.; Fischer, J.A.: Regulation of inducible and tissue-specific gene expression. Science237: 1237–1245 (1987).

    Article  Google Scholar 

  18. Dynan, W.S.; Tjian, R.: Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. Nature316: 714–718 (1985).

    Article  Google Scholar 

  19. Glass, C.K.; Holloway, J.M.; Devary, O.V.; Rosenfeld, M.G.: The thyroid hormone receptor binds with opposite transcriptional effects to a common sequence motif in thyroid hormone and estrogen receptor elements. Cell54: 313–323 (1988).

    Article  PubMed  CAS  Google Scholar 

  20. Akerblom, I.E.; Slater, E.P.; Beato, M.; Baxter, J.D.; Mellon, P.L.: Negative regulation by gluco-corticoids through interference with a cAMP responsive enhancer. Science241: 350–353 (1988).

    Article  PubMed  CAS  Google Scholar 

  21. Zinn, K.; Maniatis, T.: Detection of factors that interact with the human β-interferon regulatory region in vivo by DNase I footprinting. Cell45: 611–618 (1986).

    Article  PubMed  CAS  Google Scholar 

  22. Barberis, A.; Superti-Furga, G.; Busslinger, M.: Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter. Cell50: 347–359 (1987).

    Article  PubMed  CAS  Google Scholar 

  23. Liou, H.-C.; Polla, B.S.; Aragnol, D.; Leserman, L.D.; Griffith, I.J.; Glimcher, L.H.: A tissue-specific DNAase I-hypersensitive site in a class II Aα gene is under transregulatory control. Proc. natn. Acad. Sci. USA85: 2738–2742 (1988).

    Article  CAS  Google Scholar 

  24. Aragnol, D.; Malissen, B.; Schiff, C.; Piran, M.; Leserman, L.D.; Endocytosis of MHC molecules by B cell-B lymphoma and B cell-T lymphoma hybrids. J. Immun.137: 3347–3353 (1986).

    PubMed  CAS  Google Scholar 

  25. Griffith, I.J.; Nabavi, N.; Gohogawala, Z.; Chase, C.G.; Rodriguez, M.; McKean, D.; Glimcher, L.H.: Structural mutation affecting intracellular transport and cell surface expression of murine class II molecules. J. exp. Med.167: 541–555 (1988).

    Article  PubMed  CAS  Google Scholar 

  26. Halper, J.; Fu, S.M.; Wang, C.Y.; Winchester, R.; Kunkel, H.G.: Patterns of expression of human ‘Ia-like’ antigens during the terminal stages of B-cell development. J. Immun.120: 1480–1484 (1978).

    PubMed  CAS  Google Scholar 

  27. Kearney, J.F.; Radbruch, A.; Liesegang, G.; Rajewsky, K.: A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immun.123: 1548–1553 (1979).

    PubMed  CAS  Google Scholar 

  28. Yamamura, K.; Kitutani, H.; Folsom, V.; Clayton, L.K.; Kimoto, M.; Akira, S.; Kashiwamura, S.; Tonegawa, S.; Kishimoto, T.: Functional expression of a microinjected E dα gene in C57B116 transgenic mice. Nature316: 67–69 (1985).

    Article  PubMed  CAS  Google Scholar 

  29. LeMeur, M.; Gerlinger, P.; Benoist, C.; Mathis, D.: Correcting an immune response defect by creating Eα gene transgenic mice. Nature316: 38–42 (1985).

    Article  CAS  Google Scholar 

  30. Pinkert, C.; Widera, G.; Cowing, C.; Heber-Katz, E.; Palmiter, R.D.; Flavell, R.A.; Brinster, R.L.: Tissue-specific, inducible, and functional expression of the Eα MHC class II gene in transgenic mice. EMBO J.4: 2225–2230 (1985).

    PubMed  CAS  Google Scholar 

  31. Gillies, S.D.; Folsom, V.; Tonegawa, S.: Cell type-specific enhancer element associated with a mouse MHC gene, Eβ. Nature310: 594–597 (1984).

    Article  PubMed  CAS  Google Scholar 

  32. Korman, A.J.; Boss, J.M.; Spies, T.; Sorrentino, R.; Okada, K.; Strominger, J.L.: Genetic complexity and expression of human class II histocompatibility antigens. Immunol. Rev.85: 45–86 (1985).

    Article  PubMed  CAS  Google Scholar 

  33. O’Sullivan, D.M.; Larhammer, D.; Wilson, M.C.; Peterson, P.A.; Quaranta, V.: Structure of the human Ia-associated invariant chain gene; identification of 5′ sequences shared with major histocompatibility complex class II genes. Proc. natn. Acad. Sci. USA83: 4484–4488 (1986).

    Article  CAS  Google Scholar 

  34. Dorn, A.; Durand, B.; Marfing, C.; Le Meur, M. Benoist, C.; Mathis, D.: Conserved major histocompatibility complex class II boxes—X and Y—are transcriptional control elements and specifically bind nuclear proteins. Proc. natn. Acad. Sci. USA84: 6249–6253 (1987).

    Article  CAS  Google Scholar 

  35. Boss, J.M.; Strominger, J.: Regulation of a transfected human class II major histocompatibility complex gene in human fibroblasts. Proc. natn. Acad. Sci. USA83: 9139–9143 (1986).

    Article  CAS  Google Scholar 

  36. Koch, W.; Candeias, S.; Guardiola, J.; Accolla, R.; Benoist, C.; Mathis, D.: An enhancer factor defect in a mutant Burkitt lymphoma cell line. J. exp. Med.167: 1781–1790 (1988).

    Article  PubMed  CAS  Google Scholar 

  37. Thanos, D.; Mavrothalassitis, G.; Papametheakis, J.: Multiple regulatory regions of the 5′ side of the mouse Eα gene. Proc. natn. Acad. Sci. USA85: 3075–3079 (1988).

    Article  CAS  Google Scholar 

  38. Tsang, S.Y.; Nakanishi, M.; Peterlin, B.M.: B-cell specific and interferon-γ-inducible regulation of the HLA-DRA gene. Proc. natn. Acad. Sci. USA85: 8598–8602 (1988).

    Article  CAS  Google Scholar 

  39. Basta, P.V.; Sherman, P.A.; Ting, J.P.-Y.: Detailed delineation of an interferon-γ-responsive element important in human HLA-DRA gene expression in a glioblastoma multiforme. Proc. natn. Acad. Sci. USA85: 8618–8622 (1988).

    Article  CAS  Google Scholar 

  40. Sakurai, M.; Strominger, J.L.: B-cell-specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQβ gene. Proc. natn. Acad. Sci. USA85: 6909–6913 (1988).

    Article  CAS  Google Scholar 

  41. Sloan, J.H.; Boss, J.M.: Conserved upstream sequences of human class II major histocompatibility genes enhance expression of class II genes in wild-type but not mutant B cell lines. Proc. natn. Acad. Sci. USA85: 8186–8190 (1988).

    Article  CAS  Google Scholar 

  42. Miwa, K.; Doyle, C.; Strominger, J.L.: Sequence-specific interactions of nuclear factors with conserved sequences of human class II major histocompatibility complex genes. Proc. natn. Acad. Sci. USA83: 4939–4943 (1987).

    Article  Google Scholar 

  43. Dorn, A.; Bollekens, J.; Staub, A.; Benoist, C.; Mathis, D.: A multiplicity of CCAAT-box binding proteins. Cell50: 863–872 (1987).

    Article  PubMed  CAS  Google Scholar 

  44. Celada, A.; Shiga, M.; Imagawa, M.; Kop, J.; Maki, R.A.: Identification of a nuclear factor that binds to a conserved sequence of the I-Aβ gene. J. Immun.140: 3995–4002 (1988).

    PubMed  CAS  Google Scholar 

  45. Widera, G.; Burkly, L.C.; Pinkert, C.A.; Bottger, E.C.; Cowing, C.; Palmiter, R.D.; Brinster, R.L.; Flavell, R.A.: Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B-cells; an in vivo approach to investigate Ia gene function. Cell51: 175–187 (1987).

    Article  PubMed  CAS  Google Scholar 

  46. Van Ewijk, W.; Ron, Y.; Monaco, J.; Kappler, J.; Marrack, P.; LeMeur, M.; Gerlinger, P.; Durand, B.; Benoist, C.; Mathis, D.: Compartmentalization tion of MHC class II gene expression in transgenic mice. Cell53: 357–370 (1988).

    Article  PubMed  Google Scholar 

  47. Boothby, M.; Liou, H.-C.; Glimcher, L.H.: Differences in sequence specificity among class II MHC X box DNA binding proteins. J. Immun.142: 1005–1014 (1989).

    PubMed  CAS  Google Scholar 

  48. Liou, H.-C.; Boothby, M.; Glimcher, L.H.: Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element. Science242: 69–71 (1988).

    Article  PubMed  CAS  Google Scholar 

  49. Berk, A.J.: Adenovirus promoters and E1A transactivation. Annu. Rev. Genet.20: 45–70 (1986).

    Article  PubMed  CAS  Google Scholar 

  50. Mitchell, P.J.; Wang, C.; Tjian, R.: Positive and negative regulation of transcription in vitro: enhancer-binding protein AP-2 is inhibited by SV-40 T-antigen. Cell50: 847–861 (1987).

    Article  PubMed  CAS  Google Scholar 

  51. Yamamoto, K.K.; Gonzalez, G.A.; Biggs, W.H., III; Montminy, M.R.: Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature334: 494–498 (1988).

    Article  PubMed  CAS  Google Scholar 

  52. Snapper, C.M.; Paul, W.E.: Interferon-γ and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science236: 944–946 (1987).

    Article  PubMed  CAS  Google Scholar 

  53. Rennick, D.; Yang, G.; Muller-Sieburg, C.; Smith, C.; Arai, N.; Takabe, Y.; Gemmell, L.: Interleukin-4 can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells. Proc. natn. Acad. Sci. USA84: 6889–6893 (1987).

    Article  CAS  Google Scholar 

  54. Breathnach, R.; Chambon, P.: Organization and expression of eukaryotic split genes. Annu. Rev. Biochem.50: 349–383 (1981).

    Article  PubMed  CAS  Google Scholar 

  55. Sawadogo, M.; Roeder, R.G.: Interaction of a gene-specific transcription factor with the adenovirus major late promoter upstream of the TATA box region. Cell43: 165–175 (1985).

    Article  PubMed  CAS  Google Scholar 

  56. Gladstone, P.; Pious, D.: Identification of a transacting function regulating HLA-DR expression in a DR-negative B-cell variant. Somatic Cell Genet.6: 285–298 (1980).

    Article  PubMed  CAS  Google Scholar 

  57. Accolla, R.S.; Scarpellino, L.; Carra, G.; Guardiola, J.: Trans-acting elements operating across species barriers positively regulate expression of major histocompatibility complex class II genes. J. exp. Med.162: 1117–1133 (1985).

    Article  PubMed  CAS  Google Scholar 

  58. Reith, W.; Satola, S.; Herrero-Sanchez, C.; Amaldi, I.; Lisowska-Grospierre, B.; Griscelli, C.; Hadam, M.R.; Mach, B.: Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DRa promoter binding protein, RF-X. Cell53: 897–906 (1988).

    Article  PubMed  CAS  Google Scholar 

  59. Calman, A.F.; Peterlin, B.M.: Evidence for a trans-acting factor that regulates the transcription of class II major histocompatibility complex genes. Proc. natn. Acad. Sci. USA85: 8330–8334 (1988).

    Google Scholar 

  60. Horikoshi, M.; Hai, T.; Lin, Y.-S.; Green, M.R.; Roeder, R.G.: Transcription factor ATF interacts with the TATA factor to facilitate establishment of a preinitiation complex. Cell54: 1033–1042 (1988).

    Article  PubMed  CAS  Google Scholar 

  61. Yang, Z.; Accolla, R.S.; Pious, D.; Zegers, B.J.M.; Strominger, J.L.: Two distinct genetic loci regulating class II gene expression are defective in human mutant and patient cell lines. EMBO J.7: 1965–1972 (1988).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cancer Biology, Harvard School of Public Health, Harvard Medical School, Boston, MA, 02115, USA

    Mark Boothby, Hsiou-Chi Liou, Patricia W. Finn, Ellen Gravallese & Laurie H. Glimcher

  2. Department of Medicine, Harvard Medical School, Boston, Mass., USA

    Mark Boothby, Hsiou-Chi Liou, Patricia W. Finn, Ellen Gravallese & Laurie H. Glimcher

Authors
  1. Mark Boothby
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hsiou-Chi Liou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia W. Finn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ellen Gravallese
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurie H. Glimcher
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Boothby, M., Liou, HC., Finn, P.W. et al. Control of transcription at the murine Aα locus. Immunol Res 9, 77–92 (1990). https://doi.org/10.1007/BF02918199

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02918199

Keywords

Search

Navigation