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. 1992 Jul;12(7):3078–3086. doi: 10.1128/mcb.12.7.3078

In vivo function of regulatory DNA sequence elements of a major histocompatibility complex class I gene.

J E Maguire 1, W I Frels 1, J C Richardson 1, J D Weissman 1, D S Singer 1
PMCID: PMC364522  PMID: 1620117

Abstract

Major histocompatibility complex class I genes are expressed in nearly all somatic tissues, although their level of expression varies. By analysis of a set of promoter deletion mutants introduced into transgenic mice, a complex regulatory element, consisting of overlapping enhancer and silencer activities, is demonstrated to function as a tissue-specific regulator of class I expression. The enhancer activity predominates in lymphoid tissues but not in nonlymphoid tissues. In contrast to the tissue-specific functions of the complex regulatory element, a second novel silencer element is shown to function in both lymphoid and nonlymphoid tissues. The complement of DNA-binding factors in different cell lines is shown to correlate with the levels of class I expression.

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Selected References

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  1. Chamberlain J. W., Vasavada H. A., Ganguly S., Weissman S. M. Identification of cis sequences controlling efficient position-independent tissue-specific expression of human major histocompatibility complex class I genes in transgenic mice. Mol Cell Biol. 1991 Jul;11(7):3564–3572. doi: 10.1128/mcb.11.7.3564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci U S A. 1986 Jan;83(2):446–450. doi: 10.1073/pnas.83.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dorn A., Fehling H. J., Koch W., Le Meur M., Gerlinger P., Benoist C., Mathis D. B-cell control region at the 5' end of a major histocompatibility complex class II gene: sequences and factors. Mol Cell Biol. 1988 Oct;8(10):3975–3987. doi: 10.1128/mcb.8.10.3975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dorsett D. L., Keshet I., Winocour E. Quantitation of a simian virus 40 nonhomologous recombination pathway. J Virol. 1983 Oct;48(1):218–228. doi: 10.1128/jvi.48.1.218-228.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ehrlich R., Maguire J. E., Singer D. S. Identification of negative and positive regulatory elements associated with a class I major histocompatibility complex gene. Mol Cell Biol. 1988 Feb;8(2):695–703. doi: 10.1128/mcb.8.2.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ehrlich R., Sharrow S. O., Maguire J. E., Singer D. S. Expression of a class I MHC transgene: effects of in vivo alpha/beta-interferon treatment. Immunogenetics. 1989;30(1):18–26. doi: 10.1007/BF02421465. [DOI] [PubMed] [Google Scholar]
  8. Frels W. I., Bluestone J. A., Hodes R. J., Capecchi M. R., Singer D. S. Expression of a microinjected porcine class I major histocompatibility complex gene in transgenic mice. Science. 1985 May 3;228(4699):577–580. doi: 10.1126/science.3885396. [DOI] [PubMed] [Google Scholar]
  9. Frels W. I., Bordallo C., Golding H., Rosenberg A., Rudikoff S., Singer D. S. Expression of a class I MHC transgene: regulation by a tissue-specific negative regulatory DNA sequence element. New Biol. 1990 Nov;2(11):1024–1033. [PubMed] [Google Scholar]
  10. 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]
  11. Harris H. W., Gill T. J., 3rd Expression of class I transplantation antigens. Transplantation. 1986 Aug;42(2):109–117. doi: 10.1097/00007890-198608000-00001. [DOI] [PubMed] [Google Scholar]
  12. Israel A., Kimura A., Fournier A., Fellous M., Kourilsky P. Interferon response sequence potentiates activity of an enhancer in the promoter region of a mouse H-2 gene. Nature. 1986 Aug 21;322(6081):743–746. doi: 10.1038/322743a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Miyazaki J., Appella E., Ozato K. Negative regulation of the major histocompatibility class I gene in undifferentiated embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9537–9541. doi: 10.1073/pnas.83.24.9537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nielsen D. A., Chou J., MacKrell A. J., Casadaban M. J., Steiner D. F. Expression of a preproinsulin-beta-galactosidase gene fusion in mammalian cells. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5198–5202. doi: 10.1073/pnas.80.17.5198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Overbeek P. A., Chepelinsky A. B., Khillan J. S., Piatigorsky J., Westphal H. Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice. Proc Natl Acad Sci U S A. 1985 Dec;82(23):7815–7819. doi: 10.1073/pnas.82.23.7815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ross S. R., Graves R. A., Greenstein A., Platt K. A., Shyu H. L., Mellovitz B., Spiegelman B. M. A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9590–9594. doi: 10.1073/pnas.87.24.9590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Singer D. S., Ehrlich R. Identification of regulatory elements associated with a class I MHC gene. Curr Top Microbiol Immunol. 1988;137:148–154. doi: 10.1007/978-3-642-50059-6_22. [DOI] [PubMed] [Google Scholar]
  19. Singer D. S., Maguire J. E. Regulation of the expression of class I MHC genes. Crit Rev Immunol. 1990;10(3):235–257. [PubMed] [Google Scholar]
  20. Skoskiewicz M. J., Colvin R. B., Schneeberger E. E., Russell P. S. Widespread and selective induction of major histocompatibility complex-determined antigens in vivo by gamma interferon. J Exp Med. 1985 Nov 1;162(5):1645–1664. doi: 10.1084/jem.162.5.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Weissman J. D., Singer D. S. A complex regulatory DNA element associated with a major histocompatibility complex class I gene consists of both a silencer and an enhancer. Mol Cell Biol. 1991 Aug;11(8):4217–4227. doi: 10.1128/mcb.11.8.4217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wong G. H., Clark-Lewis I., Harris A. W., Schrader J. W. Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin. Eur J Immunol. 1984 Jan;14(1):52–56. doi: 10.1002/eji.1830140110. [DOI] [PubMed] [Google Scholar]

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