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. 1986 Oct;6(10):3550–3554. doi: 10.1128/mcb.6.10.3550

A transcriptional enhancer and an interferon-responsive sequence in major histocompatibility complex class I genes.

J Vogel, M Kress, G Khoury, G Jay
PMCID: PMC367106  PMID: 3025599

Abstract

The major histocompatibility complex class I antigens play an indispensable role in cell-cell interactions. Perturbation of their expression has been shown to have deleterious physiological consequences, including the escape of transformed cells from immune detection. In an attempt to understand how class I genes are regulated, we dissected the Ld gene to identify potential control regions. By using a test vector containing the simian virus 40 early promoter placed upstream of the bacterial chloramphenicol acetyltransferase (cat) gene, we demonstrated the presence of a transcriptional enhancer within the 5'-flanking region. The sequence is functional in both orientations and has been mapped within 350 base pairs upstream of the Ld transcriptional start site. Although human adenovirus 12 can suppress endogenous class I genes, it cannot down-regulate the activity of the transiently transfected cat gene which has been placed under the control of the Ld enhancer and promoter. Our results suggested that if the human adenovirus 12-induced function regulates the expression of class I genes by a trans mechanism, then its target site must not be within 1.9 kilobases of the 5'-flanking region. Treatment of cells with interferon increases the accumulation of class I transcripts. Expression of the cat gene under the control of the Ld enhancer and promoter also can be up-regulated by interferon. Our study shows that the target sequence required for this enhancement resides, at least in part, within the same 350-base pair segment which contains the transcriptional enhancer.

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Selected References

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

  1. Bieberich C., Scangos G., Tanaka K., Jay G. Regulated expression of a murine class I gene in transgenic mice. Mol Cell Biol. 1986 Apr;6(4):1339–1342. doi: 10.1128/mcb.6.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buc-Caron M. H., Condamine H., Jacob F. The presence of F9 antigen on the surface of mouse embryonic cells until day 8 of embryogenesis. J Embryol Exp Morphol. 1978 Oct;47:149–160. [PubMed] [Google Scholar]
  3. Cosman D., Kress M., Khoury G., Jay G. Tissue-specific expression of an unusual H-2 (class I)-related gene. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4947–4951. doi: 10.1073/pnas.79.16.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. EDIDIN M. TRANSPLANTATION ANTIGEN LEVELS IN THE EARLY MOUSE EMBRYO. Transplantation. 1964 Sep;2:627–637. doi: 10.1097/00007890-196409000-00004. [DOI] [PubMed] [Google Scholar]
  5. Evans G. A., Margulies D. H., Camerini-Otero R. D., Ozato K., Seidman J. G. Structure and expression of a mouse major histocompatibility antigen gene, H-2Ld. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1994–1998. doi: 10.1073/pnas.79.6.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fellous M., Nir U., Wallach D., Merlin G., Rubinstein M., Revel M. Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells. Proc Natl Acad Sci U S A. 1982 May;79(10):3082–3086. doi: 10.1073/pnas.79.10.3082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  8. Friedman R. L., Stark G. R. alpha-Interferon-induced transcription of HLA and metallothionein genes containing homologous upstream sequences. Nature. 1985 Apr 18;314(6012):637–639. doi: 10.1038/314637a0. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  11. Hayashi H., Tanaka K., Jay F., Khoury G., Jay G. Modulation of the tumorigenicity of human adenovirus-12-transformed cells by interferon. Cell. 1985 Nov;43(1):263–267. doi: 10.1016/0092-8674(85)90031-5. [DOI] [PubMed] [Google Scholar]
  12. Hood L., Steinmetz M., Malissen B. Genes of the major histocompatibility complex of the mouse. Annu Rev Immunol. 1983;1:529–568. doi: 10.1146/annurev.iy.01.040183.002525. [DOI] [PubMed] [Google Scholar]
  13. Hui K., Grosveld F., Festenstein H. Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984 Oct 25;311(5988):750–752. doi: 10.1038/311750a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Klein J., Figueroa F., Nagy Z. A. Genetics of the major histocompatibility complex: the final act. Annu Rev Immunol. 1983;1:119–142. doi: 10.1146/annurev.iy.01.040183.001003. [DOI] [PubMed] [Google Scholar]
  16. Kress M., Liu W. Y., Jay E., Khoury G., Jay G. Comparison of class I (H-2) gene sequences. Derivation of unique probes for members of this multigene family. J Biol Chem. 1983 Nov 25;258(22):13929–13936. [PubMed] [Google Scholar]
  17. Laimins L. A., Gruss P., Pozzatti R., Khoury G. Characterization of enhancer elements in the long terminal repeat of Moloney murine sarcoma virus. J Virol. 1984 Jan;49(1):183–189. doi: 10.1128/jvi.49.1.183-189.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lindahl P., Gresser I., Leary P., Tovey M. Interferon treatment of mice: enhanced expression of histocompatibility antigens on lymphoid cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1284–1287. doi: 10.1073/pnas.73.4.1284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mellor A. L., Golden L., Weiss E., Bullman H., Hurst J., Simpson E., James R. F., Townsend A. R., Taylor P. M., Schmidt W. Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes. Nature. 1982 Aug 5;298(5874):529–534. doi: 10.1038/298529a0. [DOI] [PubMed] [Google Scholar]
  20. Meruelo D., Nimelstein S. H., Jones P. P., Lieberman M., McDevitt H. O. Increased synthesis and expression of H-2 antigens on thymocytes as a result of radiation leukemia virus infection: a possible mechanism for H-2 linked control of virus-induced neoplasia. J Exp Med. 1978 Feb 1;147(2):470–487. doi: 10.1084/jem.147.2.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosa F., Le Bouteiller P. P., Abadie A., Mishal Z., Lemonnier F. A., Bourrel D., Lamotte M., Kalil J., Jordan B., Fellous M. HLA class I genes integrated into murine cells are inducible by interferon. Eur J Immunol. 1983 Jun;13(6):495–499. doi: 10.1002/eji.1830130612. [DOI] [PubMed] [Google Scholar]
  22. Schrier P. I., Bernards R., Vaessen R. T., Houweling A., van der Eb A. J. Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. 1983 Oct 27-Nov 2Nature. 305(5937):771–775. doi: 10.1038/305771a0. [DOI] [PubMed] [Google Scholar]
  23. Steinmetz M., Winoto A., Minard K., Hood L. Clusters of genes encoding mouse transplantation antigens. Cell. 1982 Mar;28(3):489–498. doi: 10.1016/0092-8674(82)90203-3. [DOI] [PubMed] [Google Scholar]
  24. Tanaka K., Appella E., Jay G. Developmental activation of the H-2K gene is correlated with an increase in DNA methylation. Cell. 1983 Dec;35(2 Pt 1):457–465. doi: 10.1016/0092-8674(83)90179-4. [DOI] [PubMed] [Google Scholar]
  25. Tanaka K., Isselbacher K. J., Khoury G., Jay G. Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985 Apr 5;228(4695):26–30. doi: 10.1126/science.3975631. [DOI] [PubMed] [Google Scholar]
  26. Wallich R., Bulbuc N., Hämmerling G. J., Katzav S., Segal S., Feldman M. Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature. 1985 May 23;315(6017):301–305. doi: 10.1038/315301a0. [DOI] [PubMed] [Google Scholar]
  27. Webb C. G., Gall W. E., Edelman G. M. Synthesis and distribution of H-2 antigens in preimplantation mouse embryos. J Exp Med. 1977 Oct 1;146(4):923–932. doi: 10.1084/jem.146.4.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weiss E. H., Golden L., Fahrner K., Mellor A. L., Devlin J. J., Bullman H., Tiddens H., Bud H., Flavell R. A. Organization and evolution of the class I gene family in the major histocompatibility complex of the C57BL/10 mouse. Nature. 1984 Aug 23;310(5979):650–655. doi: 10.1038/310650a0. [DOI] [PubMed] [Google Scholar]
  29. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

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