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  • Review Article
  • Published:

Epigenetic regulation in African trypanosomes: a new kid on the block

Key Points

  • Trypanosoma brucei, the causative agent of sleeping sickness in humans, diverged from the highest eukaryotic lineage several hundred million years ago. Understanding epigenetic regulation in T. brucei could shed light on important basic questions in the chromatin field.

  • Edman degradation and mass spectrometry studies revealed a striking absence of many well-conserved histone post-translational modifications (PTMs). By contrast, some unusual and apparently trypanosome-specific PTMs were identified. DNA can also carry epigenetic information, either in the form of methylcytosine or base J.

  • Consistent with a simplified histone code, the genome of T. brucei contains few candidate genes that encode for histone-modifying or chromatin-remodelling enzymes. Readers of the histone code can also be identified, and they seem to have a single PTM-binding domain.

  • Characterization of some of these epigenetic factors revealed that they are involved in the regulation of VSG monoallelic expression and cell differentiation cell cycle control.

  • Future studies should lead to the identification of more players involved in epigenetics in T. brucei, as well as the mechanistic details of how they regulate basic biological processes.

Abstract

Epigenetic regulation is important in many facets of eukaryotic biology. Recent work has suggested that the basic mechanisms underlying epigenetic regulation extend to eukaryotic parasites. The identification of post-translational histone modifications and chromatin-modifying enzymes is beginning to reveal both common and novel functions for chromatin in these parasites. In this Review, we compare the role of epigenetics in African trypanosomes and humans in several biological processes. We discuss how the study of trypanosome chromatin might help us to better understand the evolution of epigenetic processes.

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Figure 1: Chromatin structure.
Figure 2: The histone code hypothesis.
Figure 3: Sequence alignment and histone modifications of Trypanosoma brucei and human core histones.
Figure 4: Structure of the DNA modifications in Trypanosoma brucei.

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References

  1. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Strahl, B. D. & Allis, C. D. The language of covalent histone modifications. Nature 403, 41–45 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. World Health Organization. The world health report 2004 — changing history (WHO, Geneva, 2004).

  4. Engstler, M. & Boshart, M. Cold shock and regulation of surface protein trafficking convey sensitization to inducers of stage differentiation in Trypanosoma brucei. Genes Dev. 18, 2798–2811 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Urwyler, S., Studer, E., Renggli, C. K. & Roditi, I. A family of stage-specific alanine-rich proteins on the surface of epimastigote forms of Trypanosoma brucei. Mol. Microbiol. 63, 218–228 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Welstead, G. G., Schorderet, P. & Boyer, L. A. The reprogramming language of pluripotency. Curr. Opin. Genet. Dev. 18, 123–129 (2008).

    Article  CAS  PubMed  Google Scholar 

  7. Rothenberg, E. V., Moore, J. E. & Yui, M. A. Launching the T-cell-lineage developmental programme. Nature Rev. Immunol. 8, 9–21 (2008).

    Article  CAS  Google Scholar 

  8. Palenchar, J. B. & Bellofatto, V. Gene transcription in trypanosomes. Mol. Biochem. Parasitol. 146, 135–141 (2006).

    Article  CAS  PubMed  Google Scholar 

  9. Clayton, C. E. Life without transcriptional control? From fly to man and back again. EMBO J. 21, 1881–1888 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Janzen, C. J. et al. Unusual histone modifications in Trypanosoma brucei. FEBS Lett. 580, 2306–2310 (2006). This first comprehensive study of the histone PTMs in T. brucei showed that this parasite has a simplified histone code and some unusual modifications.

    Article  CAS  PubMed  Google Scholar 

  11. Mandava, V. et al. Histone modifications in Trypanosoma brucei. Mol. Biochem. Parasitol. 156, 41–50 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Saha, A., Wittmeyer, J. & Cairns, B. R. Chromatin remodelling: the industrial revolution of DNA around histones. Nature Rev. Mol. Cell Biol. 7, 437–447 (2006).

    Article  CAS  Google Scholar 

  13. Martens, J. A. & Winston, F. Recent advances in understanding chromatin remodeling by Swi/Snf complexes. Curr. Opin. Genet. Dev. 13, 136–142 (2003).

    Article  CAS  PubMed  Google Scholar 

  14. Deuring, R. et al. The ISWI chromatin-remodeling protein is required for gene expression and the maintenance of higher order chromatin structure in vivo. Mol. Cell 5, 355–365 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. de la Serna, I. L., Ohkawa, Y. & Imbalzano, A. N. Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nature Rev. Genet. 7, 461–473 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Hughes, K. et al. A novel ISWI is involved in VSG expression site downregulation in African trypanosomes. EMBO J. 26, 2400–2410 (2007). Although chromatin-remodelling activity was not definitively shown, T. brucei ISWI was the first candidate remodeller shown to be necessary to maintain fully silenced VSGs in two stages of the T. brucei life cycle.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dipaolo, C., Kieft, R., Cross, M. & Sabatini, R. Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein. Mol. Cell 17, 441–451 (2005).

    Article  CAS  PubMed  Google Scholar 

  18. Allis, C. D. et al. New nomenclature for chromatin-modifying enzymes. Cell 131, 633–636 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Ingram, A. K. & Horn, D. Histone deacetylases in Trypanosoma brucei: two are essential and another is required for normal cell cycle progression. Mol. Microbiol. 45, 89–97 (2002). This pioneering study of histone-modifying enzymes in T. brucei showed that, despite substantial evolutionary divergence, four histone deacetylases in T. brucei have conserved features with those of higher eukaryotes.

    Article  CAS  PubMed  Google Scholar 

  20. Kawahara, T. et al. Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes. Mol. Microbiol. 69, 1054–1068 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Siegel, T. N. et al. Acetylation of histone H4K4 is cell cycle regulated and mediated by HAT3 in Trypanosoma brucei. Mol. Microbiol. 67, 762–771 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Alsford, S., Kawahara, T., Isamah, C. & Horn, D. A sirtuin in the African trypanosome is involved in both DNA repair and telomeric gene silencing but is not required for antigenic variation. Mol. Microbiol. 63, 724–736 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Garcia-Salcedo, J. A., Gijon, P., Nolan, D. P., Tebabi, P. & Pays, E. A chromosomal SIR2 homologue with both histone NAD-dependent ADP-ribosyltransferase and deacetylase activities is involved in DNA repair in Trypanosoma brucei. EMBO J. 22, 5851–5862 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cloos, P. A., Christensen, J., Agger, K. & Helin, K. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease. Genes Dev. 22, 1115–1140 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Bedford, M. T. & Clarke, S. G. Protein arginine methylation in mammals: who, what, and why. Mol. Cell 33, 1–13 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wysocka, J., Allis, C. D. & Coonrod, S. Histone arginine methylation and its dynamic regulation. Front. Biosci. 11, 344–355 (2006).

    Article  CAS  PubMed  Google Scholar 

  27. Pelletier, M., Pasternack, D. A. & Read, L. K. In vitro and in vivo analysis of the major type I protein arginine methyltransferase from Trypanosoma brucei. Mol. Biochem. Parasitol. 144, 206–217 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Pasternack, D. A., Sayegh, J., Clarke, S. & Read, L. K. Evolutionarily divergent type II protein arginine methyltransferase in Trypanosoma brucei. Eukaryot. Cell 6, 1665–1681 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fisk, J. C. et al. A type III protein arginine methyltransferase from the protozoan parasite, Trypanosoma brucei. J. Biol. Chem. 284, 11590–11600 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lowell, J. E. & Cross, G. A. A variant histone H3 is enriched at telomeres in Trypanosoma brucei. J. Cell Sci. 117, 5937–5947 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Lowell, J. E., Kaiser, F., Janzen, C. J. & Cross, G. A. Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA in Trypanosoma brucei. J. Cell Sci. 118, 5721–5730 (2005). This was the first time that the histone variant H2AZ was shown to associate with a novel variant H2B.

    Article  CAS  PubMed  Google Scholar 

  32. Alsford, S. & Horn, D. Trypanosomatid histones. Mol. Microbiol. 53, 365–372 (2004).

    Article  CAS  PubMed  Google Scholar 

  33. Sullivan, W. J. Jr, Naguleswaran, A. & Angel, S. O. Histones and histone modifications in protozoan parasites. Cell. Microbiol. 8, 1850–1861 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Thatcher, T. H. & Gorovsky, M. A. Phylogenetic analysis of the core histones H2A, H2B, H3, and H4. Nucleic Acids Res. 22, 174–179 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. da Cunha, J. P., Nakayasu, E. S., de Almeida, I. C. & Schenkman, S. Post-translational modifications of Trypanosoma cruzi histone H4. Mol. Biochem. Parasitol. 150, 268–277 (2006).

    Article  CAS  PubMed  Google Scholar 

  36. Latham, J. A. & Dent, S. Y. Cross-regulation of histone modifications. Nature Struct. Mol. Biol. 14, 1017–1024 (2007).

    Article  CAS  Google Scholar 

  37. Briggs, S. D. et al. Gene silencing: trans-histone regulatory pathway in chromatin. Nature 418, 498 (2002).

    Article  CAS  PubMed  Google Scholar 

  38. Sun, Z. W. & Allis, C. D. Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 418, 104–108 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Mandava, V., Janzen, C. J. & Cross, G. A. Trypanosome H2Bv replaces H2B in nucleosomes enriched for H3 K4 and K76 trimethylation. Biochem. Biophys. Res. Commun. 368, 846–851 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hyland, E. M. et al. Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae. Mol. Cell. Biol. 25, 10060–10070 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Shilatifard, A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu. Rev. Biochem. 75, 243–269 (2006).

    Article  CAS  PubMed  Google Scholar 

  42. Steger, D. J. et al. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Mol. Cell. Biol. 28, 2825–2839 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. San-Segundo, P. A. & Roeder, G. S. Role for the silencing protein Dot1 in meiotic checkpoint control. Mol. Biol. Cell 11, 3601–3615 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Huyen, Y. et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432, 406–411 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Janzen, C. J., Hake, S. B., Lowell, J. E. & Cross, G. A. M. Selective di- or trimethylation of histone H3 lysine 76 by two DOT1 homologs is important for cell cycle regulation in Trypanosoma brucei. Mol. Cell 23, 497–507 (2006). This paper is the first study of the enzymatic activity of KMTs in trypanosomes and also describes the importance of the DOT1 homologues in cell cycle control.

    Article  CAS  PubMed  Google Scholar 

  46. Grant, P. A. & Berger, S. L. Histone acetyltransferase complexes. Semin. Cell Dev. Biol. 10, 169–177 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Tachibana, M. et al. G9a histone methyltransferase plays a dominant role in euchromatic histone H3 lysine 9 methylation and is essential for early embryogenesis. Genes Dev. 16, 1779–1791 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Brownell, J. E. & Allis, C. D. Special HATs for special occasions: linking histone acetylation to chromatin assembly and gene activation. Curr. Opin. Genet. Dev. 6, 176–184 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Sterner, D. E. & Berger, S. L. Acetylation of histones and transcription-related factors. Microbiol. Mol. Biol. Rev. 64, 435–459 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Siegel, T. N. et al. Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei. Genes Dev. 23, 1063–1076 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Schotta, G. et al. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes Dev. 18, 1251–1262 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Schotta, G. et al. A chromatin-wide transition to H4K20 monomethylation impairs genome integrity and programmed DNA rearrangements in the mouse. Genes Dev. 22, 2048–2061 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Donati, G. et al. An NF-Y-dependent switch of positive and negative histone methyl marks on CCAAT promoters. PLoS ONE 3, e2066 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ruthenburg, A. J., Li, H., Patel, D. J. & Allis, C. D. Multivalent engagement of chromatin modifications by linked binding modules. Nature Rev. Mol. Cell Biol. 8, 983–994 (2007).

    Article  CAS  Google Scholar 

  55. Taverna, S. D., Li, H., Ruthenburg, A. J., Allis, C. D. & Patel, D. J. How chromatin-binding modules interpret histone modifications: lessons from professional pocket pickers. Nature Struct. Mol. Biol. 14, 1025–1040 (2007).

    Article  CAS  Google Scholar 

  56. Colot, V. & Rossignol, J. L. Eukaryotic DNA methylation as an evolutionary device. Bioessays 21, 402–411 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Robertson, K. D. DNA methylation and human disease. Nature Rev. Genet. 6, 597–610 (2005).

    CAS  PubMed  Google Scholar 

  58. Rojas, M. V. & Galanti, N. DNA methylation in Trypanosoma cruzi. FEBS Lett. 263, 113–116 (1990).

    Article  CAS  PubMed  Google Scholar 

  59. Militello, K. T. et al. African trypanosomes contain 5-methylcytosine in nuclear DNA. Eukaryot. Cell 7, 2012–2016 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gommers-Ampt, J. H. et al. β-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei. Cell 75, 1129–1136 (1993). This paper describes the chemical structure of base J, a DNA modification that has not been found in other organisms.

    Article  CAS  PubMed  Google Scholar 

  61. Borst, P. & Sabatini, R. Base J: discovery, biosynthesis, and possible functions. Annu. Rev. Microbiol. 62, 235–251 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Kieft, R. et al. JBP2, a SWI2/SNF2-like protein, regulates de novo telomeric DNA glycosylation in bloodstream form Trypanosoma brucei. Mol. Biochem. Parasitol. 156, 24–31 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Yu, Z. et al. The protein that binds to DNA base J in trypanosomatids has features of a thymidine hydroxylase. Nucleic Acids Res. 35, 2107–2115 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Cliffe, L. J. et al. JBP1 and JBP2 are two distinct thymidine hydroxylases involved in J biosynthesis in genomic DNA of African trypanosomes. Nucleic Acids Res. 37, 1452–1462 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Genest, P. A. et al. Formation of linear inverted repeat amplicons following targeting of an essential gene in Leishmania. Nucleic Acids Res. 33, 1699–1709 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. McStay, B. & Grummt, I. The Epigenetics of rRNA genes: from molecular to chromosome biology. Annu. Rev. Cell Dev. Biol. 24, 131–157 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Berriman, M. et al. The genome of the African trypanosome Trypanosoma brucei. Science 309, 416–422 (2005).

    Article  CAS  PubMed  Google Scholar 

  68. Alsford, S., Kawahara, T., Glover, L. & Horn, D. Tagging a T. brucei RRNA locus improves stable transfection efficiency and circumvents inducible expression position effects. Mol. Biochem. Parasitol. 144, 142–148 (2005).

    Article  CAS  PubMed  Google Scholar 

  69. Waters, A. P., Syin, C. & McCutchan, T. F. Developmental regulation of stage-specific ribosome populations in Plasmodium. Nature 342, 438–440 (1989).

    Article  CAS  PubMed  Google Scholar 

  70. Waters, A. P. et al. Species-specific regulation and switching of transcription between stage-specific ribosomal RNA genes in Plasmodium berghei. J. Biol. Chem. 272, 3583–3589 (1997).

    Article  CAS  PubMed  Google Scholar 

  71. McCracken, S. et al. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription. Nature 385, 357–361 (1997).

    Article  CAS  PubMed  Google Scholar 

  72. Kooter, J. M. & Borst, P. α-amanitin-insensitive transcription of variant surface glycoprotein genes provides further evidence for discontinuous transcription in trypanosomes. Nucleic Acids Res. 12, 9457–9472 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Rudenko, G., Bishop, D., Gottesdiener, K. & Van der Ploeg, L. H. α-amanitin resistant transcription of protein coding genes in insect and bloodstream form Trypanosoma brucei. EMBO J. 8, 4259–4263 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hertz-Fowler, C. et al. Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS ONE 3, e3527 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Navarro, M. & Gull, K. A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414, 759–763 (2001). The observation that the actively transcribed VSG localizes in a discrete non-nucleolar structure that contains RNA polymerase I and is resistant to DNase I treatment allowed the emergence of a new model in which allelic exclusion was achieved by limiting the location of VSG genes in the nuclear space.

    Article  CAS  PubMed  Google Scholar 

  76. Landeira, D. & Navarro, M. Nuclear repositioning of the VSG promoter during developmental silencing in Trypanosoma brucei. J. Cell Biol. 176, 133–139 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Scherf, A. et al. Antigenic variation in malaria: in situ switching, relaxed and mutually exclusive transcription of var genes during intra-erythrocytic development in Plasmodium falciparum. EMBO J. 17, 5418–5426 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Chess, A., Simon, I., Cedar, H. & Axel, R. Allelic inactivation regulates olfactory receptor gene expression. Cell 78, 823–834 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Brandenburg, J. et al. Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex. EMBO J. 26, 4856–4866 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Grune, T. et al. Crystal structure and functional analysis of a nucleosome recognition module of the remodeling factor ISWI. Mol. Cell 12, 449–460 (2003).

    Article  PubMed  Google Scholar 

  81. Sandell, L. L., Gottschling, D. E. & Zakian, V. A. Transcription of a yeast telomere alleviates telomere position effect without affecting chromosome stability. Proc. Natl Acad. Sci. USA 91, 12061–12065 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Freitas-Junior, L. H. et al. Telomeric heterochromatin propagation and histone acetylation control mutually exclusive expression of antigenic variation genes in malaria parasites. Cell 121, 25–36 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Figueiredo, L. M., Janzen, C. J. & Cross, G. A. A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biol 6, e161 (2008). This paper showed that DOT1B is necessary for rapid VSG switching, demonstrating for the first time the importance of a histone-modifying enzyme for antigenic variation in African trypanosomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Li, B., Espinal, A. & Cross, G. A. M. Trypanosome telomeres are protected by a homologue of mammalian TRF2. Mol. Cell. Biol. 25, 5011–5021 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yang, X., Figueiredo, L. M., Espinal, A., Okubo, E. & Li, B. RAP1 is essential for silencing telomeric Variant Surface Glycoprotein genes in Trypanosoma brucei. Cell 137, 99–109 (2009). RAP1 is the first telomeric protein that, when disrupted, shows a phenotype clearly related to VSG gene regulation, confirming the importance of telomeres during antigenic variation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Margueron, R., Trojer, P. & Reinberg, D. The key to development: interpreting the histone code? Curr. Opin.t Genet. Dev. 15, 163–176 (2005).

    Article  CAS  Google Scholar 

  87. Schlimme, W., Burri, M., Bender, K., Betschart, B. & Hecker, H. Trypanosoma brucei brucei: differences in the nuclear chromatin of bloodstream forms and procyclic culture forms. Parasitology 107, 237–247 (1993). Hecker et al . present some groundbreaking findings on chromatin structure in trypanosomes, including the biochemical properties of chromatin in two stages of the T. brucei life cycle.

    Article  PubMed  Google Scholar 

  88. Burri, M., Schlimme, W., Betschart, B. & Hecker, H. Characterization of the histones of Trypanosoma brucei brucei bloodstream forms. Acta Trop. 58, 291–305 (1994).

    Article  CAS  PubMed  Google Scholar 

  89. Rout, M. P. & Field, M. C. Isolation and characterization of subnuclear compartments from Trypanosoma brucei. Identification of a major repetitive nuclear lamina component. J. Biol. Chem. 276, 38261–38271 (2001).

    Article  CAS  PubMed  Google Scholar 

  90. Ziegelbauer, K., Quinten, M., Schwarz, H., Pearson, T. W. & Overath, P. Synchronous differentiation of Trypanosoma brucei from bloodstream to procyclic forms in vitro. Eur. J. Biochem. 192, 373–378 (1990).

    Article  CAS  PubMed  Google Scholar 

  91. Ogbadoyi, E., Ersfeld, K., Robinson, D., Sherwin, T. & Gull, K. Architecture of the Trypanosoma brucei nucleus during interphase and mitosis. Chromosoma 108, 501–513 (2000).

    Article  CAS  PubMed  Google Scholar 

  92. Hammarton, T. C. Cell cycle regulation in Trypanosoma brucei. Mol. Biochem. Parasitol. 153, 1–8 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hirumi, H. & Hirumi, K. Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers. J. Parasitol. 75, 985–989 (1989).

    Article  CAS  PubMed  Google Scholar 

  94. Carruthers, V. B. & Cross, G. A. High-efficiency clonal growth of bloodstream- and insect-form Trypanosoma brucei on agarose plates. Proc. Natl Acad. Sci. USA 89, 8818–8821 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. LaCount, D. J., Bruse, S., Hill, K. L. & Donelson, J. E. Double-stranded RNA interference in Trypanosoma brucei using head-to-head promoters. Mol. Biochem. Parasitol. 111, 67–76 (2000).

    Article  CAS  PubMed  Google Scholar 

  96. Wang, Z., Morris, J. C., Drew, M. E. & Englund, P. T. Inhibition of Trypanosoma brucei gene expression by RNA interference using an integratable vector with opposing T7 promoters. J. Biol. Chem. 275, 40174–40179 (2000).

    Article  CAS  PubMed  Google Scholar 

  97. Scahill, M. D., Pastar, I. & Cross, G. A. CRE recombinase-based positive-negative selection systems for genetic manipulation in Trypanosoma brucei. Mol. Biochem. Parasitol. 157, 73–82 (2008).

    Article  CAS  PubMed  Google Scholar 

  98. Pays, E. Regulation of antigen gene expression in Trypanosoma brucei. Trends Parasitol. 21, 517–520 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Scherf, A., Lopez-Rubio, J. J. & Riviere, L. Antigenic variation in Plasmodium falciparum. Annu. Rev. Microbiol. 62, 445–470 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Buck, L. & Axel, R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65, 175–187 (1991).

    Article  CAS  PubMed  Google Scholar 

  101. Voss, T. S. et al. A var gene promoter controls allelic exclusion of virulence genes in Plasmodium falciparum malaria. Nature 439, 1004–1008 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Lopez-Rubio, J. J. et al. 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites. Mol. Microbiol. 66, 1296–1305 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Nguyen, M. Q., Zhou, Z., Marks, C. A., Ryba, N. J. & Belluscio, L. Prominent roles for odorant receptor coding sequences in allelic exclusion. Cell 131, 1009–1017 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Frank, M. et al. Strict pairing of var promoters and introns is required for var gene silencing in the malaria parasite Plasmodium falciparum. J. Biol. Chem. 281, 9942–9952 (2006).

    Article  CAS  PubMed  Google Scholar 

  105. Klose, R. J. & Zhang, Y. Regulation of histone methylation by demethylimination and demethylation. Nature Rev. Mol. Cell Biol. 8, 307–318 (2007).

    Article  CAS  Google Scholar 

  106. Amiguet-Vercher, A. et al. Loss of the mono-allelic control of the VSG expression sites during the development of Trypanosoma brucei in the bloodstream. Mol. Microbiol. 51, 1577–1588 (2004).

    Article  CAS  PubMed  Google Scholar 

  107. Dean, S., Marchetti, R., Kirk, K. & Matthews, K. R. A surface transporter family conveys the trypanosome differentiation signal. Nature 459, 213–217 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank S. Hake and N. Siegel for their critical reading of the manuscript; G. Rudenko and R. Sabatini for helpful comments; and P. Bastin and B. Rotureau for providing micrographs of the different stages of the T. brucei life cycle, which were used, in part, to draw the cartoons in Table 1.

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Correspondence to Luisa M. Figueiredo.

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DATABASES

Entrez Genome Project

Caenorhabditis elegans

Saccharomyces cerevisiae

Trypanosoma brucei

FURTHER INFORMATION

George A. M. Cross's homepage

Pfam

PlasmoDB

Smart

TriTrypDB

Glossary

Post-translational modification

An enzymatic modification of an amino acid residue that occurs after a protein is synthesized, and often modifies the function or lifespan of a protein.

Variant surface glycoprotein

(VSG). The most abundant protein (approximately 10 million identical copies on individual cells) at the surface of the bloodstream slender, stumpy and metacyclic life cycle stages of Trypanosoma brucei. Periodic change of the VSG surface coat is a crucial part of the evasion mechanism known as antigenic variation.

Tsetse

The insect vector (Glossina spp.) that ensures the transmission of Trypanosoma brucei between two mammalian hosts. The word tsetse means fly and it originates from the Tswana language.

Procyclin

The most abundant protein at the surface of the procyclic life cycle form. There are two types of procyclin: EP and GPEET. These glycosylated proteins are not subject to allelic exclusion.

Epimastigote

The Trypanosoma brucei life cycle stage that colonizes the tsetse salivary glands.

Metacyclic

The Trypanosoma brucei life cycle stage in the tsetse salivary glands that reinfects the mammalian host.

Edman degradation

A method developed by P. Edman to sequence peptides by sequential labelling and cleavage of single residues from the amino-terminal end of polypeptides.

Euchromatin

A form of chromatin that was first defined as lightly stained nuclear regions by light microscopy and is usually associated with transcriptionally competent chromosome loci.

Heterochromatin

A more compact form of chromatin that, when using light or electron microscopy, appears as darker regions of the nucleus. Heterochromatinis usually associated with transcriptionally silent chromosome loci.

Antigenic variation

The process by which an infectious organism alters its surface to evade the host immune response; common in several pathogens, such as Trypanosoma brucei, the malaria parasite Plasmodium falciparum and Giardia lamblia.

Monoallelic expression

The expression of a single allele from a gene family.

Triton acid urea gel electrophoresis

A polyacrylamide gel-based electrophoresis technique that allows the efficient separation of core histones as a result of their association with Triton X- 100.

Karyokinesis

The process that partitions of the nucleus into the daughter cells during cell division.

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Figueiredo, L., Cross, G. & Janzen, C. Epigenetic regulation in African trypanosomes: a new kid on the block. Nat Rev Microbiol 7, 504–513 (2009). https://doi.org/10.1038/nrmicro2149

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