Abstract
The POU family transcription factor Oct-2 was originally identified in B lymphocytes but has been shown to be expressed in neuronal cells, although it is absent in most other cell types. Cotransfection of Oct-2 expression vectors into nonneuronal cells with a tyrosine hydroxylase promoter/reporter plasmid suggests that Oct-2 can repress this promoter in this artificial situation. Here we report that reduction of endogenous Oct-2 levels in a neuronal cell line by an antisense approach results in an increase in endogenous tyrosine hydroxylase levels. In contrast, the level of the neuronal marker protein PGP9.5 remains unchanged in the antisense lines whereas that of the neuronal nitric oxide synthase decreases. Hence, the tyrosine hydroxylase gene is a natural target for repression by Oct-2 in neuronal cells. The significance of this effect is discussed in terms of the processes that regulate tyrosine hydroxylase gene expression and the role of Oct-2 in neuronal cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bjorklund A. and Hokfelt T. (eds.) (1984)Handbook of Chemical Neuroanatomy Classical Transmitters in the CNS, Part 1., Elsevier, Amsterdam.
Bovolenta C., Tognon M., and Liboi E. (1991) Epidermal growth factor induces in the EL alpha 4-2 cell line, herpes simplex virus-1 alpha 4 gene transcription in the absence of the viral transactivator VP16.Virus Res. 19, 199–208.
Dawson S. J., Yoon S. O., Chikaraishi D. M., Lillycrop K. A., and Latchman D. S. (1994) The Oct-2 transcription factor represses tyrosine hydroxylase expression via the heptamer motif in the promoter.Nucleic Acids Res. 22, 1023–1028.
Dent C. L., Lillycrop K. A., Estridge J. K., Thomas N. S. B., and Latchman D. S. (1991) The B cell and neuronal forms of the octamer binding protein Oct-2 differ in DNA binding specificity and functional activity.Mol. Cell. Biol. 11, 3925–3930.
Dhillon V. B., McCallum S., Norton P. M., Erkeller-Yuksel F., Lydyard P., Isenberg D. A., and Latchman D. S. (1993) Differential heat shock protein overexpression and its clinical relevance in systemic lupus erythematosis.Ann. Rheum. Dis. 52, 436–442.
Falkner F. G., Moickat R., and Zachau H. G. (1986) Sequences closely related to an immunoglobulin promoter/enhancer element occur also upstream of other eukaryotic and of prokaryotic genes.Nucleic Acids Res. 13, 7847–7863.
Gerster T., Matthias P., Thali M., Jiriciny J., and Schaffner W. (1987) Cell type-specificity of the immunoglobulin heavy chain gene enhancer.EMBO J. 6, 1323–1330.
Gill G. and Ptashne M. (1988) Negative effect of the transcriptional activator GAL4.Nature 334, 721–724.
Gorman C. M. (1985) High efficiency gene transfer into mammalian cells, inDNA Cloning, A Practical Approach (Glover D. M., ed.), IRL, Oxford, UK, pp. 143–190.
He X., Treacy M. N., Simmons D. M., Ingraham H. A., Swanson L. S., and Rosenfeld M. G. (1989) Expression of a large family of POU-domain regulatory genes in mammalian brain development.Nature 340, 35–42.
Katz D. M. (1991) A catecholaminergic sensory neuron phenotype in cranial derivatives of the neural crest: regulation by cell aggregation and nerve growth factor.J. Neurosci. 11, 3991–4002.
Kemp L. M., Dent C. L., and Latchman D. S. (1990) Transcriptional repression of herpes simplex virus immediate early genes and of octamer-containing cellular promoters in neuronal cells is mediated by the octamer DNA element.Neuron 4, 215–222.
Latchman D. S. (1990) Molecular biology of Herpes simplex virus latency.J. Exp. Pathol. 71, 133–141.
Latchman D. S. (1995)Gene Regulation: A Eukaryotic Perspective, 2nd ed. Chapman and Hall, London.
Lewis E. J., Harrington C. A., and Chikaraishi D. M. (1987) Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.Proc. Natl. Acad. Sci. USA 84, 3550–3554.
Lewis E. J. and Chikaraishi D. M. (1987) Regulated expression of the tyrosine hydroxylase gene by epidermal growth factor.Mol. Cell. Biol. 7, 3332–3336.
Lillycrop K. A., Dent C. L., Wheatley S. C., Beech M. N., Ninkina N. N., Wood J. N., and Latchman D. S. (1991) The octamer binding protein Oct-2 represses HSV immediate early genes in cell lines derived from latently infectable sensory neurons.Neuron 7, 381–390.
Lillycrop K. A., Dawson S. J., Estridge J. K., Gerster T., Matthias P., and Latchman D. S. (1994) Repression of a herpes simplex virus immediate-early promoter by the Oct-2 transcription factor is dependent upon an inhibitory region at the N-terminus of the protein.Mol. Cell. Biol. 14, 7633–7642.
Lillycrop K. A. and Latchman D. S. (1992) Alternative splicing of the Oct-2 transcription factor is differentially regulated in B cells and neuronal cells and results in protein isoforms with opposite effects on the activity of octamer/TAA TGARAT-containing promoters.J. Biol. Chem. 267, 24,960–24,966.
Masserano J. M. and Weiner N. (1983) Tyrosine hydroxylase and regulation in the central nervous system.Mol. Cell. Biol. 53, 129–152.
Morgenstern J. P. and Land H. (1990) A series of mammalian expression vectors and characterization of their expression of a reporter gene in stably and transiently transfected cells.Nucleic Acids Res. 18, 1068.
Parslour T. G., Blair D. L., Murphy W. J., and Grammer D. K. (1984) Structure of the 5′ ends of immunoglobulin genes: a novel conserved sequence.Proc. Natl. Acad. Sci. USA 81, 2650–2654.
Pfisterer P., Annweiler A., Ulmer C., Corcoran L. M., and Wirth T. (1994) Differential transactivation potential of Oct-1 and Oct-2 is determined by additional B cell-specific activities.EMBO J. 13, 1654–1663.
Roizman B. and Sears A. E. (1987) An inquiry into the mechanisms of herpes simplex virus latency.Ann. Rev. Microbiol. 41, 543–571.
Scholer H. R., Hatzopoulos A. K., and Balling R. (1989) A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor.EMBO J. 8, 2543–2550.
Singh H., Sen R., Baltimore D., and Sharp P. A. (1986) A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes.Nature 319, 154–158.
Springall D. R., Riveros-Moreno V., Buttery L., Suburo A., Bishop A. E., Merrett M., Moncada S., and Polak J. M. (1992) Immunological detection of nitric oxide synthase (s) in human tissues using heterologous antibodies suggesting different isoforms.Histochemistry 98, 259–266.
Stachowiak M. K., Sebbane R., Stricker E. M., Zigmond M. J., and Kaplan B. B. (1985) Effect of chronic cold exposure on tyrosine hydroxylase mRNA in rat adrenal gland.Brain Res. 359, 356–359.
Staudt L. H., Singh H., Sen R., Wirth T., Sharp P. A., and Baltimore D. (1986) A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes.Nature 323, 640–643.
Stoykova A. S., Steiner S., Erselius J. R., Hatzopoulos A. K., and Grass P. (1992) Mini-Oct and Oct-2c: two novel functionally diverse murine Oct-2 products are differentially expressed in the CNS.Neuron 841, 541–558.
Suburo A. M., Wheatley S. C., Horn D. A., Gibson S. J., Jahn R., Fischer-Colbrie R., et al. (1992) Intracellular redistribution of neuropeptides and secretory proteins during differentiation of neuronal cell lines.Neuroscience 46, 881–889.
Thoenen H. (1970) Induction of tyrosine hydroxylase in peripheral and central adrenergic neurons by cold exposure of rats.Nature 228, 861,862.
Verrijzer C. P. and van der Vliet P. C. (1993) POU domain transcription factors.Biochim. Biophys. Acta 1173, 1–21.
Wegner M., Drolet D. W., and Rosenfeld M. G. (1993) POU-domain proteins: structure and function of developmental regulators.Curr. Opin. Cell Biol. 5, 488–498.
Wheatley S. C., Dent C. L., Wood J. N., and Latchman D. S. (1992) Elevation of cyclic AMP levels in cell lines derived from latently infectable sensory neurons increases their permissivity for herpes virus infection by activating the viral immediate-early 1 gene promoter.Brain Res. 12, 149–154.
Wirth T., Staudt L., and Baltimore D. (1987) An Octamer oligonucleotide upstream of a TATA motif is sufficient for lymphoid specific promoter activity.Nature 329, 176–178.
Wirth T., Priess A., Annweiler A., Zwilling S., and Oeler B. (1991) Multiple Oct-2 isoforms are generated by alternative splicing.Nucleic Acids Res. 19, 43–51.
Wood J. N., Lillycrop K. A., Dent C. L., Ninkina N. N., Beech M. N., Willoughby J. J., Winter J., and Latchman D. S. (1992) Regulation of expression of the neuronal POU protein Oct-2 by nerve growth factor.J. Biol. Chem. 267, 17,787–17,791.
Yoon S. O. and Chikaraishi D. M. (1992) Tissue-specific transcription of the rat tyrosine hydroxylase gene requires synergy between an AP1 motif and an overlapping E box-containing dyad.Neuron 9, 55–67.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Deans, Z., Dawson, S.J., Buttery, L. et al. Direct evidence that the POU family transcription factor Oct-2 represses the cellular tyrosine hydroxylase gene in neuronal cells. J Mol Neurosci 6, 159–167 (1995). https://doi.org/10.1007/BF02736762
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02736762