Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1998 Feb 15;330(Pt 1):155–161. doi: 10.1042/bj3300155

Transcriptional regulation of MHC class I gene expression in rat oligodendrocytes.

G Mavria 1, K T Hall 1, R A Jones 1, G E Blair 1
PMCID: PMC1219121  PMID: 9461504

Abstract

MHC class I molecules are normally expressed at very low levels in the brain and their up-regulation in response to cytokines and viral infections has been associated with a number of neurological disorders. Here we demonstrate that the down-regulation of surface class I molecules in differentiated primary rat oligodendrocytes was accompanied by reduced steady-state levels of class I heavy-chain mRNA. Transient expression assays were performed in oligodendrocytes and fibroblasts, using a mouse H-2Kb class I promoter chloramphenicol acetyltransferase plasmid termed pH2KCAT (which contained 5'-flanking sequences from -2033 to +5 bp of the H-2Kb gene relative to the transcriptional start site at +1 bp). These assays showed that H-2Kb promoter activity was reduced in oligodendrocytes but not in class I-expressing fibroblasts. H-2Kb promoter activity was up-regulated in oligodendrocytes co-transfected with a plasmid expression vector encoding the transcriptional activator tax of human T-cell leukaemia virus type I, showing that down-regulation of promoter activity was reversible. Deletion mutant analysis of the H-2Kb promoter revealed the presence of negative regulatory elements that were functional in oligodendrocytes at -1.61 to -1.07 kb and -242 to -190 bp. Deletion of sequences in pH2KCAT encompassing the downstream element totally abolished promoter activity in both oligodendrocytes and fibroblasts, whereas a deletion within the upstream negative regulatory element increased promoter activity specifically in oligodendrocytes. The upstream negative regulatory element also down-regulated a linked heterologous herpes simplex virus thymidine kinase promoter in oligodendrocytes, but not in fibroblasts. Gel retardation assays using overlapping DNA probes that spanned the entire -1.61 to -1.07 kb region revealed the presence of a number of DNA-binding activities that were present in oligodendrocyte, but not in fibroblast nuclear extracts.

Full Text

The Full Text of this article is available as a PDF (386.5 KB).

Selected References

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

  1. Achim C. L., Wiley C. A. Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy. J Neuropathol Exp Neurol. 1992 May;51(3):257–263. doi: 10.1097/00005072-199205000-00003. [DOI] [PubMed] [Google Scholar]
  2. Asipu A., Blair G. E. Regulation of myelin basic protein-encoding gene transcription in rat oligodendrocytes. Gene. 1994 Dec 15;150(2):227–234. doi: 10.1016/0378-1119(94)90431-6. [DOI] [PubMed] [Google Scholar]
  3. Baldwin A. S., Jr, Sharp P. A. Binding of a nuclear factor to a regulatory sequence in the promoter of the mouse H-2Kb class I major histocompatibility gene. Mol Cell Biol. 1987 Jan;7(1):305–313. doi: 10.1128/mcb.7.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burke P. A., Hirschfeld S., Shirayoshi Y., Kasik J. W., Hamada K., Appella E., Ozato K. Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene. J Exp Med. 1989 Apr 1;169(4):1309–1321. doi: 10.1084/jem.169.4.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Henson J. W. Regulation of the glial-specific JC virus early promoter by the transcription factor Sp1. J Biol Chem. 1994 Jan 14;269(2):1046–1050. [PubMed] [Google Scholar]
  6. Hirt B. Replicating molecules of polyoma virus DNA. J Mol Biol. 1969 Feb 28;40(1):141–144. doi: 10.1016/0022-2836(69)90302-7. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Joly E., Mucke L., Oldstone M. B. Viral persistence in neurons explained by lack of major histocompatibility class I expression. Science. 1991 Sep 13;253(5025):1283–1285. doi: 10.1126/science.1891717. [DOI] [PubMed] [Google Scholar]
  9. Kenney S., Natarajan V., Strike D., Khoury G., Salzman N. P. JC virus enhancer-promoter active in human brain cells. Science. 1984 Dec 14;226(4680):1337–1339. doi: 10.1126/science.6095453. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Kralli A., Ge R., Graeven U., Ricciardi R. P., Weinmann R. Negative regulation of the major histocompatibility complex class I enhancer in adenovirus type 12-transformed cells via a retinoic acid response element. J Virol. 1992 Dec;66(12):6979–6988. doi: 10.1128/jvi.66.12.6979-6988.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kraus E., Schneider-Schaulies S., Miyasaka M., Tamatani T., Sedgwick J. Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infection: evidence for the role of type-1 interferon. Eur J Immunol. 1992 Jan;22(1):175–182. doi: 10.1002/eji.1830220126. [DOI] [PubMed] [Google Scholar]
  13. Levine B., Hardwick J. M., Trapp B. D., Crawford T. O., Bollinger R. C., Griffin D. E. Antibody-mediated clearance of alphavirus infection from neurons. Science. 1991 Nov 8;254(5033):856–860. doi: 10.1126/science.1658936. [DOI] [PubMed] [Google Scholar]
  14. Lindsley M. D., Patick A. K., Prayoonwiwat N., Rodriguez M. Coexpression of class I major histocompatibility antigen and viral RNA in central nervous system of mice infected with Theiler's virus: a model for multiple sclerosis. Mayo Clin Proc. 1992 Sep;67(9):829–838. doi: 10.1016/s0025-6196(12)60820-9. [DOI] [PubMed] [Google Scholar]
  15. Liu X., Ge R., Westmoreland S., Cooney A. J., Tsai S. Y., Tsai M. J., Ricciardi R. P. Negative regulation by the R2 element of the MHC class I enhancer in adenovirus-12 transformed cells correlates with high levels of COUP-TF binding. Oncogene. 1994 Aug;9(8):2183–2190. [PubMed] [Google Scholar]
  16. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Martin J. D., King D. M., Slauch J. M., Frisque R. J. Differences in regulatory sequences of naturally occurring JC virus variants. J Virol. 1985 Jan;53(1):306–311. doi: 10.1128/jvi.53.1.306-311.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Martin M. E., Piette J., Yaniv M., Tang W. J., Folk W. R. Activation of the polyomavirus enhancer by a murine activator protein 1 (AP1) homolog and two contiguous proteins. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5839–5843. doi: 10.1073/pnas.85.16.5839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Massa P. T., Brinkmann R., ter Meulen V. Inducibility of Ia antigen on astrocytes by murine coronavirus JHM is rat strain dependent. J Exp Med. 1987 Jul 1;166(1):259–264. doi: 10.1084/jem.166.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Massa P. T., Ozato K., McFarlin D. E. Cell type-specific regulation of major histocompatibility complex (MHC) class I gene expression in astrocytes, oligodendrocytes, and neurons. Glia. 1993 Jul;8(3):201–207. doi: 10.1002/glia.440080307. [DOI] [PubMed] [Google Scholar]
  21. Mauerhoff T., Pujol-Borrell R., Mirakian R., Bottazzo G. F. Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain. J Neuroimmunol. 1988 Jul;18(4):271–289. doi: 10.1016/0165-5728(88)90049-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mellor A. L. Molecular genetics of class I genes in the mammalian major histocompatibility complex. Oxf Surv Eukaryot Genes. 1986;3:95–140. [PubMed] [Google Scholar]
  23. Minty A. J., Alonso S., Guénet J. L., Buckingham M. E. Number and organization of actin-related sequences in the mouse genome. J Mol Biol. 1983 Jun 15;167(1):77–101. doi: 10.1016/s0022-2836(83)80035-7. [DOI] [PubMed] [Google Scholar]
  24. Piette J., Yaniv M. Molecular analysis of the interaction between an enhancer binding factor and its DNA target. Nucleic Acids Res. 1986 Dec 22;14(24):9595–9611. doi: 10.1093/nar/14.24.9595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Proffitt J. L., Sharma E., Blair G. E. Adenovirus 12-mediated down-regulation of the major histocompatibility complex (MHC) class I promoter: identification of a negative regulatory element responsive to Ad12 E1A. Nucleic Acids Res. 1994 Nov 11;22(22):4779–4788. doi: 10.1093/nar/22.22.4779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roach A., Boylan K., Horvath S., Prusiner S. B., Hood L. E. Characterization of cloned cDNA representing rat myelin basic protein: absence of expression in brain of shiverer mutant mice. Cell. 1983 Oct;34(3):799–806. doi: 10.1016/0092-8674(83)90536-6. [DOI] [PubMed] [Google Scholar]
  27. Ruijs T. C., Freedman M. S., Grenier Y. G., Olivier A., Antel J. P. Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes. J Neuroimmunol. 1990 May;27(2-3):89–97. doi: 10.1016/0165-5728(90)90058-U. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Satoh J., Kim S. U., Kastrukoff L. F., Takei F. Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes. J Neurosci Res. 1991 May;29(1):1–12. doi: 10.1002/jnr.490290102. [DOI] [PubMed] [Google Scholar]
  29. Sawada M., Suzumura A., Yoshida M., Marunouchi T. Human T-cell leukemia virus type I trans activator induces class I major histocompatibility complex antigen expression in glial cells. J Virol. 1990 Aug;64(8):4002–4006. doi: 10.1128/jvi.64.8.4002-4006.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schnitzer J., Schachner M. Expression of Thy-1, H-2, and NS-4 cell surface antigens and tetanus toxin receptors in early postnatal and adult mouse cerebellum. J Neuroimmunol. 1981 Dec;1(4):429–456. doi: 10.1016/0165-5728(81)90022-9. [DOI] [PubMed] [Google Scholar]
  31. Segars J. H., Nagata T., Bours V., Medin J. A., Franzoso G., Blanco J. C., Drew P. D., Becker K. G., An J., Tang T. Retinoic acid induction of major histocompatibility complex class I genes in NTera-2 embryonal carcinoma cells involves induction of NF-kappa B (p50-p65) and retinoic acid receptor beta-retinoid X receptor beta heterodimers. Mol Cell Biol. 1993 Oct;13(10):6157–6169. doi: 10.1128/mcb.13.10.6157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Silverman T., Rein A., Orrison B., Langloss J., Bratthauer G., Miyazaki J., Ozato K. Establishment of cell lines from somite stage mouse embryos and expression of major histocompatibility class I genes in these cells. J Immunol. 1988 Jun 15;140(12):4378–4387. [PubMed] [Google Scholar]
  33. Sun D., Meyermann R., Wekerle H. Cytotoxic T cells in autoimmune disease of the central nervous system. Ann N Y Acad Sci. 1988;532:221–229. doi: 10.1111/j.1749-6632.1988.tb36341.x. [DOI] [PubMed] [Google Scholar]
  34. Suzumura A., Lavi E., Weiss S. R., Silberberg D. H. Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. Science. 1986 May 23;232(4753):991–993. doi: 10.1126/science.3010460. [DOI] [PubMed] [Google Scholar]
  35. Suzumura A., Silberberg D. H. Expression of H-2 antigen on oligodendrocytes is induced by soluble factors from concanavalin A activated T cells. Brain Res. 1985 Jun 10;336(1):171–175. doi: 10.1016/0006-8993(85)90431-7. [DOI] [PubMed] [Google Scholar]
  36. Suzumura A., Silberberg D. H., Lisak R. P. The expression of MHC antigens on oligodendrocytes: induction of polymorphic H-2 expression by lymphokines. J Neuroimmunol. 1986 May;11(3):179–190. doi: 10.1016/0165-5728(86)90002-0. [DOI] [PubMed] [Google Scholar]
  37. Traugott U. Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol. 1987 Oct;16(2):283–302. doi: 10.1016/0165-5728(87)90082-8. [DOI] [PubMed] [Google Scholar]
  38. Turnley A. M., Morahan G., Okano H., Bernard O., Mikoshiba K., Allison J., Bartlett P. F., Miller J. F. Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. Nature. 1991 Oct 10;353(6344):566–569. doi: 10.1038/353566a0. [DOI] [PubMed] [Google Scholar]
  39. Weiss E., Golden L., Zakut R., Mellor A., Fahrner K., Kvist S., Flavell R. A. The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens. EMBO J. 1983;2(3):453–462. doi: 10.1002/j.1460-2075.1983.tb01444.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Williams K. A., Hart D. N., Fabre J. W., Morris P. J. Distribution and quantitation of HLA-ABC and DR (Ia) antigens on human kidney and other tissues. Transplantation. 1980 Apr;29(4):274–279. doi: 10.1097/00007890-198004000-00002. [DOI] [PubMed] [Google Scholar]
  41. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]
  42. Wong G. H., Bartlett P. F., Clark-Lewis I., McKimm-Breschkin J. L., Schrader J. W. Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells. J Neuroimmunol. 1985 Feb-Mar;7(5-6):255–278. doi: 10.1016/s0165-5728(84)80026-0. [DOI] [PubMed] [Google Scholar]
  43. Yoshioka T., Feigenbaum L., Jay G. Transgenic mouse model for central nervous system demyelination. Mol Cell Biol. 1991 Nov;11(11):5479–5486. doi: 10.1128/mcb.11.11.5479. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES