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Cytosine demethylation in the tyrosine hydroxylase gene promoter in hypothalamus cells of rat brain under the action of 2-aminoadamantane compound Ladasten

  • Animal Genetics
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Abstract

In our previous study of mechanisms of pharmacological activity of a derivative of 2-aminoadamantane, Ladasten, we have shown more than a twofold increase in the mRNA level of the tyrosine hydroxylase (TH) gene in the rat brain hypothalamus 1.5–2.0 h after a single administration of this substance. In the present study, we employed the bisulfate sequencing technique to detect changes of GpG islands methylation status in the TH gene 5′-flanking region (−650)−(+84) in hypothalamus cells of control and experimental rats after a single exposure to Ladasten. Ladasten was shown to increase frequency of cytosine demethylation in binding sites of some transcription factors or in neighboring motifs. It is suggested that the Ladasten-induced increase of TH gene transcriptional activity in rat hypothalamus is associated with cytosine demethylation in CpG islands in some regulatory gene elements.

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References

  1. Morozov, I.S., Artsimovich, I.G., and Fadeeva, T.A., Soviet Union Patent No. 1826906, Byull. Izobr., 1993. 25. 97.

  2. Vakhitova, Yu.V., Yamidanov, R.S., and Seredenin, S.B., Ladasten Induces Expression of the Genes, Governing Dopamine Biosynthesis in Various Rat Brain Structures, Eksper. Klin. Farmakol., 2004, vol. 67, no. 4, pp. 7–11.

    Google Scholar 

  3. Kumer, S.C. and Vrana, E.K., Intricate Regulation of Tyrosine Hydroxylase Activity and Gene Expression, J. Neurochem., 1996, vol. 67, pp. 443–462.

    Article  PubMed  CAS  Google Scholar 

  4. Yang, C., Kim, H.S., Seo, H., et al., Identification and Characterization of Potential cis-Regulatory Elements Governing Transcriptional Activation of the Rat Tyrosine Hydroxylase Gene, J. Neurochem., 1998, vol. 71, pp. 1358–1368.

    Article  PubMed  CAS  Google Scholar 

  5. Nagamoto-Combs, K., Piech, K.M., Best, J.A., et al., Tyrosine Hydroxylase Gene Promoter Activity Is Regulated by Both Cyclic AMP-Responsive Element and AP 1 Sites Following Calcium Influx, J. Biol. Chem., 1997, vol. 272, pp. 6051–6058.

    Article  PubMed  CAS  Google Scholar 

  6. Kim, K.S., Kim, C.U., Hwang, D.Y., et al., The Orphan Nuclear Receptor Nurr1 Directly Transactivates the Promoter of the Tyrosine Hydroxylase Gene, but the Dopamine β-Hydroxylase Gene, in a Cell-Specific Manner, J. Neurochem., 2003, vol. 85, pp. 622–634.

    Article  PubMed  CAS  Google Scholar 

  7. Okuse, K., Matsuoka, J., and Kurihara, K., Tissue-Specific Methylation Occurs in the Essential Promoter Element of the Tyrosine Hydroxylase Gene, Mol. Brain Res., 1997, vol. 46, pp. 197–207.

    Article  PubMed  CAS  Google Scholar 

  8. Vanyushin, B.F., Enzymatic DNA Methylation—Epigenetic Control of Genetic Cell Functions, Biokhimiya, 2005, vol. 70, no. 5, pp. 598–611.

    Google Scholar 

  9. Attwood, J.T., Yung, R.L., and Richardson, B.C., DNA Methylation and the Regulation of Gene Transcription, Cell Mol. Life Sci., 2002, vol. 59, pp. 241–257.

    Article  PubMed  CAS  Google Scholar 

  10. Razin, A., CpG Methylation, Chromatin Structure and Gene Silencing—a Three-Way Connection, EMBO J., 1998, vol. 17, pp. 4905–4908.

    Article  PubMed  CAS  Google Scholar 

  11. Nan, X., Ng, H.H., Johnson, C.A., et al., Transcriptional Repression by the Methyl-CpG-Binding Protein MeCP2 Involves a Histone Deacetylase Complex, Nature, 1998, vol. 393, pp. 386–389.

    Article  PubMed  CAS  Google Scholar 

  12. Prendergast, G.C. and Ziff, E.B., Methylation-Sensitive Sequence-Specific DNA Binding by the c-Myc Basic Region, Science, 1991, vol. 251, pp. 186–189.

    PubMed  CAS  Google Scholar 

  13. Ramchandani S., Bhattacharya S.K., Cervoni N., et al., DNA Methylation Is a Reversible Biological Signal, Proc. Natl Acad. Sci. USA., 1999. vol. 96. pp. 6107–6112.

    Article  PubMed  CAS  Google Scholar 

  14. Cardoso, M.C. and Leonhardt, H., DNA Methyltransferase Is Actively Retained in the Cytoplasm during Early Development, J. Cell Biol., 1999, vol. 147, pp. 25–32.

    Article  PubMed  CAS  Google Scholar 

  15. Shyf, M., Methylation and Demethylation of DNA as a Target of Anticancer Therapy, Biokhimiya, 2005, vol. 70, no. 5, pp. 651–669.

    Google Scholar 

  16. Zhu, B., Benjamin, D., Zheng, Y., et al., Overexpression of 5-Methylcytosine DNA Glycosylase in Human Embryonic Kidney Cells EcR293 Demethylates the Promoter of a Hormone-Regulated Reporter Gene, Proc. Natl Acad. Sci. USA., 2001, vol. 98, pp. 5031–5036.

    Article  PubMed  CAS  Google Scholar 

  17. Detich, N., Theberge, J., and Szyf, M., Promoter-Specific Activation and Demethylation by MBD2/Demethylase, J. Biol. Chem., 2002, vol. 277, no. 39, pp. 35791–35794.

    Article  PubMed  CAS  Google Scholar 

  18. Chiurazzi, P. and Neri, G., Pharmacological Reactivation of Inactive Genes: The Fragile X Experience, Brain Res. Bull, 2001, vol. 56, nos. 3–4, pp. 383–387.

    Article  PubMed  CAS  Google Scholar 

  19. Nyce, J.W., Drug-Induced DNA Hypermethylation: A Potential Mediator of Acquired Drug Resistance during Cancer Chemotherapy, Mutat. Res., 1997, vol. 386, pp. 153–161.

    Article  PubMed  CAS  Google Scholar 

  20. Wyczechowska, D. and Fabianowska-Majewska, K.V., The Effects of Cladribine and Fludarabine on DNA Methylation in K522 Cells, Biochem. Pharmacol., 2003, vol. 65, pp. 219–225.

    Article  PubMed  CAS  Google Scholar 

  21. Villar-Garea, A. and Esteller, M., DNA Demethylating Agents and Chromatin-Remodelling Drugs: Which, How and Why?, Curr. Drug Metab., 2003, vol. 4, no. 1, pp. 11–31.

    Article  PubMed  CAS  Google Scholar 

  22. Morozov, I.S., Petrov, V.I., and Sergeeva, S.A., Farmakologiya adamantanov (Pharmacology of Adamantanes), Volgograd, 2001.

  23. Sambrook, J., Fritsch, E., and Maniatis, T., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Lab., 1989.

    Google Scholar 

  24. Frommer, M., McDonald, L., Millar, D., et al., A Genomic Sequencing Protocol That Yields a Positive Display of 5-Methylcytosine Residues in Individual DNA Strands, Proc. Natl. Acad. Sci. USA, 1992, vol. 89, pp. 1827–1831.

    Article  PubMed  CAS  Google Scholar 

  25. Bender, C.M., Zingg, J.-M., and Jones, P.A., DNA Methylation As a Target for Drug Design, Pharm. Res, 1998, vol. 15, pp. 175–187.

    Article  PubMed  CAS  Google Scholar 

  26. Szyf, M., Towards a Pharmacology of DNA Methylation, TRENDS Pharm. Sci, 2001, vol. 22, pp. 350–354.

    Article  PubMed  CAS  Google Scholar 

  27. Lin, X., Asgari, K., Putzi, M.J., et al., Reversal of GSTP1 CpG Island Hypermethylation and Reactivation of GSTP1 Expression in Human Prostate Cancer Cells by Treatment with Procainamide, Cancer Res., 2001, vol. 61, pp. 8611–8616.

    PubMed  CAS  Google Scholar 

  28. Zambrano, P., Segura-Pacheco, B., Perez-Cardenas, E., et al., A Phase I Study of Hydralazine To Demethylate and Reactivate the Expression of Tumor Suppressor Genes, BMC Cancer, 2005, vol. 5, p. 1186.

    Article  CAS  Google Scholar 

  29. Lee, W.S., Shim, J.Y., and Zhu, B.T., Mechanisms for the Inhibition of DNA Methyltransferases by Tea Catechins and Bioflavonoids, Mol. Pharmacol., 2005, vol. 68, no. 4, pp. 1018–1030.

    Article  PubMed  CAS  Google Scholar 

  30. Lee, W.S. and Zhu, B.T., Inhibition of DNA Methylation by Caffeic Acid and Chlorogenic Acid, Two Common Catechol-Containing Coffee Polyphenols, Carcinogenesis, 2006, vol. 27, pp. 269–277.

    Article  PubMed  CAS  Google Scholar 

  31. Marks, P.A., Richon, V.M., Breslow, R., et al., Histone Deacetylase Inhibitors as New Cancer Drugs, Curr. Opin. Oncol., 2001, vol. 13, pp. 477–483.

    Article  PubMed  CAS  Google Scholar 

  32. Detich, N., Bovenzi, V., and Szif, M., Valproate Induces Replication—Independent Active DNA Demethylation, J. Biol. Chem., 2003, vol. 278, pp. 27586–27592.

    Article  PubMed  CAS  Google Scholar 

  33. Kim, H.-S., Park, J.-S., Hong, S.-J., et al., Regulation of the Tyrosine Hydroxylase Gene Promoter by Histone Deacetylase Inhibitors, Biochem. Biophys. Res. Commun., 2003, vol. 312, no. 4, pp. 950–995.

    Article  PubMed  CAS  Google Scholar 

  34. Cervoni, N. and Szyf, M., Demethylase Activity Is Directed by Histone Acetylation, J. Biol. Chem., 2001, vol. 276, pp. 40778–40787.

    Article  PubMed  CAS  Google Scholar 

  35. Li, J., Guo, Y., Schroeder, F.A., et al., Dopamine D2-Like Antagonists Induce Chromatin Remodeling in Striatal Neurons Through Cyclic AMP-Protein Kinase A and NMDA Receptor Signaling, J. Neurochem., 2004, vol. 90, pp. 1117–1131.

    Article  PubMed  CAS  Google Scholar 

  36. Thomassin, H., Flavin, M., Espinas, M.-L., et al., Glucocorticoid-Induced DNA Demethylation and Gene Memory during Development, EMBO J., 2001, vol. 20, pp. 1974–1983.

    Article  PubMed  CAS  Google Scholar 

  37. Kress, C., Thomassin, H., and Grange, T., Local DNA Demethylation in Vertebrates: How Could It Be Performed and Targeted?, FEBS Lett., 2001, vol. 494, pp. 135–140.

    Article  PubMed  CAS  Google Scholar 

  38. Irvine, R.A., Lin, I.G., and Hsieh, C.-L., DNA Methylation Has a Local Effect on Transcription and Histone Acetylation, Mol. Cell. Biol., 2002, vol. 22, no. 19, pp. 6689–6696.

    Article  PubMed  CAS  Google Scholar 

  39. Curradi, M., Izzo, A., and Badaracco, G., Molecular Mechanisms of Gene Silencing Mediated by DNA Methylation, Mol. Cell. Biol., 2002, vol. 22, no. 9, pp. 3157–3173.

    Article  PubMed  CAS  Google Scholar 

  40. Smet, Ch.De., Loriot, A., and Boon, T., Promoter-Dependent Mechanism Leading To Selective Hypomethylation within the 5′ Region of Gene MAGE—A1 in Tumor Cells, Mol. Cell. Biol., 2004, vol. 24, pp. 4781–4790.

    Article  PubMed  CAS  Google Scholar 

  41. Best, J.A., Chen, Y., Piech, K.M., et al., The Response of the Tyrosine Hydroxylase Gene To Cyclic AMP Is Mediated by Two Cyclic AMP Response Elements, J. Neurochem., 1995, vol. 65, pp. 1934–1943.

    Article  PubMed  CAS  Google Scholar 

  42. Sheng, M., McFadden, G., and Greenberg, M.E., Membrane Depolarization and Calcium Induce C-Fos Transcription Via Phosphorylation of Transcription Factor CREB, Neuron, 1990, vol. 4, pp. 571–582.

    Article  PubMed  CAS  Google Scholar 

  43. Okuse, K., Mizuno, N., Matsuoka, I., et al., Induction of Cholinergic and Adrenergic Differentiation in N-18 Cells by Differentiation Agents and DNA Demethylating Agents, Brain Res., 1993, vol. 626, pp. 225–233.

    Article  PubMed  CAS  Google Scholar 

  44. Aranyi, T., Faucheux, B.A., Khalfalla, O., et al., The Tissue-Specific Methylation of the Human Tyrosine Hydroxylase Gene Reveals New Regulatory Elements in the Firs Exon, J. Neurochem., 2005, vol. 94, pp. 129–139.

    Article  PubMed  CAS  Google Scholar 

  45. Vakhitova, Yu.V., Salimgareeva, M.Kh., and Seredenin, S.B., The Effect of Ladastene on the Activity of cAMP-Dependent Protein Kinases and Protein Phosphorylation in Rat Brain Cells, Eksper. Klinich. Farmakol., 2004, vol. 67, no. 3, pp. 7–9.

    Google Scholar 

  46. Vakhitova, Yu.V., Salimgareeva, M.Kh., and Seredenin, S.B., The Effect of Ladastene on Protein Kinase C Activity in Rat Brain Cells, Eksper. Klinich. Farmakol., 2004, vol. 67, no. 2, pp. 12–15.

    CAS  Google Scholar 

  47. Kim, H.S., Hong, S.J., LeDoux, M.S., et al., Regulation of the Tyrosine and Dopamine Hydroxylase Genes by the Transcription Factor AP-2, J. Neurochem., 2001, vol. 76, pp. 280–294.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 450054, Russia

    Yu. V. Vakhitova, S. V. Sadovnikov & R. S. Yamidanov

  2. Zakusov State Research Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, 125315, Russia

    Yu. V. Vakhitova & S. B. Seredenin

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  1. Yu. V. Vakhitova
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  2. S. V. Sadovnikov
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  3. R. S. Yamidanov
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  4. S. B. Seredenin
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Original Russian Text © Yu.V. Vakhitova, S.V. Sadovnikov, R.S. Yamidanov, S.B. Seredenin, 2006, published in Genetika, 2006, Vol. 42, No. 7, pp. 968–975.

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Vakhitova, Y.V., Sadovnikov, S.V., Yamidanov, R.S. et al. Cytosine demethylation in the tyrosine hydroxylase gene promoter in hypothalamus cells of rat brain under the action of 2-aminoadamantane compound Ladasten. Russ J Genet 42, 795–801 (2006). https://doi.org/10.1134/S1022795406070155

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  • DOI: https://doi.org/10.1134/S1022795406070155

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