Deacetylation of histones is required for gene regulation and cell cycle progression and the mediators, the histone deacetylases, are being vigorously pursued as drug targets for cancer chemotherapy. The deacetylases are also potential drug targets against infectious diseases and genome sequencing revealed proteins of this class in each of three kinetoplastid parasites. These enzymes are now being characterised and assessed for chemotherapeutic potential.


Histone Deacetylase Hydroxamic Acid Histone Deacetylase Inhibitor Potential Drug Target Trypanosoma Brucei 
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  1. 1.
    Taunton J, Hassig CA, Schreiber SL. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 1996; 272:408–11.PubMedCrossRefGoogle Scholar
  2. 2.
    Hubbert C, Guardiola A, Shao R et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002; 417:455–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Ivens AC, Peacock CS, Worthey EA et al. The genome of the kinetoplastid parasite, Leishmania major. Science 2005; 309:436–42.PubMedCrossRefGoogle Scholar
  4. 4.
    Shogren-Knaak M, Ishii H, Sun JM et al. Histone H4-K16 acetylation controls chromatin structure and protein interactions. Science 2006; 311:844–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Loyola A, Almouzni G. Bromodomains in living cells participate in deciphering the histone code. Trends Cell Biol 2004; 14:279–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Pflum M, Tong J, Lane W et al. Histone deacetylase I phosphorylation promotes enzymatic activity and complex formation. J Biol Chem 2001; 276:47733–41.PubMedCrossRefGoogle Scholar
  7. 7.
    McKinsey TA, Zhang CL, Lu J et al. Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation. Nature 2000; 408:106–11.PubMedCrossRefGoogle Scholar
  8. 8.
    Yang L, Mei Q, Zielinska-Kwiatkowska A et al. An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription corepressors mSin3A/B. Biochem J 2003; 369:651–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Pile L, Schlag E, Wassarman D. The SIN3/RPD3 deacetylase complex is essential for G2 phase cell cycle progression and regulation of SMRTER corepressor levels. Mol Cell Biol 2002; 22:4965–76.PubMedCrossRefGoogle Scholar
  10. 10.
    Blander G, Guarente L. The sir2 family of protein deacetylases. Annu Rev Biochem 2004; 73:417–35.PubMedCrossRefGoogle Scholar
  11. 11.
    Grubisha O, Smith BC, Denu JM. Small molecule regulation of Sir2 protein deacetylases. Febs J 2005; 272:4607–16.PubMedCrossRefGoogle Scholar
  12. 12.
    Ingram AK, Horn D. Histone deacetylases in Trypanosoma brucei: Two are essential and another is required for normal cell cycle progression. Mol Microbiol 2002; 45:89–97.PubMedCrossRefGoogle Scholar
  13. 13.
    Dokmanovic M, Marks PA. Prospects: Histone deacetylase inhibitors. J Cell Biochem 2005; 96:293–304.PubMedCrossRefGoogle Scholar
  14. 14.
    Johnstone RW. Histone-deacetylase inhibitors: Novel drugs for the treatment of cancer. Nat Rev Drug Discov 2002; 1:287–99.PubMedCrossRefGoogle Scholar
  15. 15.
    Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: Novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays 1995; 17:423–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Darkin-Rattray SJ, Gurnett AM, Myers RW et al. Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA 1996; 93:13143–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Taddei A, Roche D, Bickmore WA et al. The effects of histone deacetylase inhibitors on heterochromatin: Implications for anticancer therapy? EMBO Rep 2005; 6:520–4.PubMedCrossRefGoogle Scholar
  18. 18.
    Van Lint C, Emiliani S, Verdin E. The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expr 1996; 5:245–53.PubMedGoogle Scholar
  19. 19.
    Ekwall K, Olsson T, Turner BM et al. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell 1997; 91:1021–32.PubMedCrossRefGoogle Scholar
  20. 20.
    Eissenberg JC, Elgin SC. Antagonizing the neighbours. Nature 2005; 438:1090–1.PubMedCrossRefGoogle Scholar
  21. 21.
    Andrews KT, Walduck A, Kelso MJ et al. Anti-malarial effect of histone deacetylation inhibitors and mammalian tumour cytodifferentiating agents. Int J Parasitol 2000; 30:761–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Murray PJ, Kranz M, Ladlow M et al. The synthesis of cyclic tetrapeptoid analogues of the antiprotozoal natural product apicidin. Bioorg Med Chem Lett 2001; 11:773–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Rundlett SE, Carmen AA, Kobayashi R et al. HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. Proc Natl Acad Sci USA 1996; 93:14503–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Finnin MS, Donigian JR, Cohen A et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999; 401:188–93.PubMedCrossRefGoogle Scholar
  25. 25.
    Somoza JR, Skene RJ, Katz BA et al. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure 2004; 12:1325–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Glover L, Horn D. Repression of polymerase I-mediated gene expression at Trypanosoma brucei telomeres. EMBO Rep 2006; 7:93–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Baur J, Zou Y, Shay J et al. Telomere position effect in human cells. Science 2001; 292:2075–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Horn, D. Nuclear gene transcription and chromatin in Trypanosoma brucei. Int J Parasitol 2001; 31:1157–65.PubMedCrossRefGoogle Scholar
  29. 29.
    Wu J, Carmen AA, Kobayashi R et al. HDA2 and HDA3 are related proteins that interact with and are essential for the activity of the yeast histone deacetylase HDA1. Proc Natl Acad Sci USA 2001; 98:4391–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 1997; 18:2714–23.PubMedCrossRefGoogle Scholar
  31. 31.
    Sayle RA, Milner White EJ. RASMOL: Biomolecular graphics for all. Trends Biochem Sci 1995; 20:374–6.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • David Horn
    • 1
  1. 1.London School of Hygiene & Tropical MedicineUK

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