Abstract
Trypanosoma brucei is a unicellular protozoan transmitted by Glossina spp. (“tsetse”) flies and the causative agent of Human African trypanosomiasis. This parasite is famous for undergoing antigenic variation, one of the most sophisticated strategies to escape the immune response of its mammalian hosts. Antigenic variation depends on the tight control of the expression of variant surface glycoproteins (VSGs), which form a dense coat that covers the parasite. To perform antigenic variation, T. brucei needs to meet two essential requirements: (1) to express a single VSG gene, among a genetic repertoire of ~2000 members, and (2) to periodically switch the expressed VSG gene. In recent years, several chromatin-associated factors have been found to be important to control VSG gene expression. This chapter focuses on the epigenetic regulation of gene expression in T. brucei, particularly in antigenic variation.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- Tb:
-
Trypanosoma brucei
- ASF1A, ASF1B:
-
Anti-silencing factor 1A, 1B
- BES:
-
Bloodstream expression site
- BSF:
-
Bloodstream form
- BDF3:
-
Bromodomain factor 3
- CAF-1b:
-
Chromatin assembly factor 1b
- CenH3:
-
Centromere-specific histone H3 variant
- CITFA:
-
Class I transcription factor A
- ChIP:
-
Chromatin immunoprecipitation
- DAC1-3:
-
Histone deacetylase 1-3
- DOT1A, DOT1B:
-
Disruptor of telomeric silencing 1A, 1B
- ELP3b:
-
Elongator protein 3b
- ESAG:
-
Expression site-associated gene
- ESB:
-
Expression site body
- FACT:
-
Facilitates chromatin transcription complex
- FYRP:
-
Phenylalanine/tyrosine rich protein
- GPI:
-
Glycosylphosphatidylinositol
- HAT:
-
Human African trypanosomiasis
- HAT1-3:
-
Histone acetyltransferase 1-3
- ISWI:
-
Imitation switch chromatin remodeler
- J:
-
β-D-glucosyl-hydroxymethyluracil
- JBP1-2:
-
J binding protein 1-2
- JGT:
-
Base J-associated glucosyltransferase
- Ku70/Ku80:
-
Ku heterodimer
- MCM-BP:
-
Mini-chromosome maintenance-binding protein
- NLP:
-
Nucleoplasmin-like protein
- NUP-1:
-
Nuclear lamin-like protein
- ORC1:
-
Origin replication complex 1/cell division cycle 6-like protein
- PIP5K:
-
Phosphatidylinositol, 5-kinase
- PIP5Pase:
-
Phosphatidylinositol 5-phosphatase
- Pol I, Pol II:
-
RNA polymerase I, II
- PTM:
-
Posttranslational modification
- PTU:
-
Polycistronic transcription unit
- RAP1:
-
Repressor/activator of protein 1
- RCCP:
-
Regulator of chromosome condensation 1-like protein
- rDNA:
-
Ribosomal DNA
- RRM1:
-
RNA recognition motif-containing protein
- SIR2rp1:
-
Silent information regulator 2-related protein 1
- SIZ1:
-
SUMO E3 ligase
- TDP-1:
-
Trypanosome DNA-binding protein
- TERT:
-
Telomerase reverse transcriptase
- TIF2:
-
TRF-interacting factor 2
- TRF:
-
Telomeric repeat-binding factor
- TSS:
-
Transcription start site
- TTS:
-
Transcription termination site
- VSG:
-
Variant surface glycoprotein
References
Akiyoshi B, Gull K (2014) Discovery of unconventional kinetochores in kinetoplastids. Cell 156(6):1247–1258. doi:10.1016/j.cell.2014.01.049
Alsford S, duBois K, Horn D, Field MC (2012) Epigenetic mechanisms, nuclear architecture and the control of gene expression in trypanosomes. Expert Rev Mol Med 14:e13. doi:10.1017/erm.2012.7
Alsford S, Horn D (2011) Elongator protein 3b negatively regulates ribosomal DNA transcription in african trypanosomes. Mol Cell Biol 31(9):1822–1832. doi:10.1128/MCB.01026-10
Alsford S, Horn D (2012) Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei. Nucleic Acids Res. doi:10.1093/nar/gks813
Alsford S, Kawahara T, Isamah C, Horn D (2007) 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(3):724–736. doi:10.1111/j.1365-2958.2006.05553.x
Amit-Avraham I, Pozner G, Eshar S, Fastman Y, Kolevzon N, Yavin E, Dzikowski R (2015) Antisense long noncoding RNAs regulate var gene activation in the malaria parasite Plasmodium falciparum. Proc Natl Acad Sci U S A 112(9):E982–E991. doi:10.1073/pnas.1420855112
Aresta-Branco F, Pimenta S, Figueiredo LMA (2016) A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei. Nucleic Acids Res 44(7):3131–3146
Batram C, Jones NG, Janzen CJ, Markert SM, Engstler M (2014) Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei. elife 3:e02324
Benmerzouga I, Concepcion-Acevedo J, Kim HS, Vandoros AV, Cross GA, Klingbeil MM, Li B (2013) Trypanosoma brucei Orc1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching. Mol Microbiol 87(1):196–210. doi:10.1111/mmi.12093
Berriman M, Ghedin E, Hertz-Fowler C, Blandin G, Renauld H, Bartholomeu DC, Lennard NJ, Caler E, Hamlin NE, Haas B, Bohme U, Hannick L et al (2005) The genome of the African trypanosome Trypanosoma brucei. Science 309(5733):416–422. doi:10.1126/science.1112642
Black SJ, Guirnalda P, Frenkel D, Haynes C, Bockstal V (2010) Induction and regulation of Trypanosoma brucei VSG-specific antibody responses. Parasitology 137(14):2041–2049. doi:10.1017/S003118200999165X
Brun R, Blum J, Chappuis F, Burri C (2010) Human African trypanosomiasis. Lancet 375(9709):148–159. doi:10.1016/S0140-6736(09)60829-1
Bullard W, Lopes da Rosa-Spiegler J, Liu S, Wang Y, Sabatini R (2014) Identification of the glucosyltransferase that converts hydroxymethyluracil to base J in the trypanosomatid genome. J Biol Chem 289(29):20273–20282. doi:10.1074/jbc.M114.579821
Cavalier-Smith T (2010) Kingdoms Protozoa and Chromista and the eozoan root of the eukaryotic tree. Biol Lett 6(3):342–345. doi:10.1098/rsbl.2009.0948
Cestari I, Stuart K (2015) Inositol phosphate pathway controls transcription of telomeric expression sites in trypanosomes. Proc Natl Acad Sci U S A 112(21):E2803–E2812. doi:10.1073/pnas.1501206112
Chaves I, Rudenko G, Dirks-Mulder A, Cross M, Borst P (1999) Control of variant surface glycoprotein gene-expression sites in Trypanosoma brucei. EMBO J 18(17):4846–4855. doi:10.1093/emboj/18.17.4846
Chaves I, Zomerdijk J, Dirks-Mulder A, Dirks RW, Raap AK, Borst P (1998) Subnuclear localization of the active variant surface glycoprotein gene expression site in Trypanosoma brucei. Proc Natl Acad Sci U S A 95(21):12328–12333
Cliffe LJ, Siegel TN, Marshall M, Cross GA, Sabatini R (2010) Two thymidine hydroxylases differentially regulate the formation of glucosylated DNA at regions flanking polymerase II polycistronic transcription units throughout the genome of Trypanosoma brucei. Nucleic Acids Res 38(12):3923–3935. doi:10.1093/nar/gkq146
Conway C, McCulloch R, Ginger ML, Robinson NP, Browitt A, Barry JD (2002) Ku is important for telomere maintenance, but not for differential expression of telomeric VSG genes, in African trypanosomes. J Biol Chem 277(24):21269–21277. doi:10.1074/jbc.M200550200
Croken MM, Nardelli SC, Kim K (2012) Chromatin modifications, epigenetics, and how protozoan parasites regulate their lives. Trends Parasitol 28(5):202–213. doi:10.1016/j.pt.2012.02.009
Cross GA (1975) Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71(3):393–417
Cross M, Kieft R, Sabatini R, Dirks-Mulder A, Chaves I, Borst P (2002) J-binding protein increases the level and retention of the unusual base J in trypanosome DNA. Mol Microbiol 46(1):37–47
Cross GA, Kim HS, Wickstead B (2014) Capturing the variant surface glycoprotein repertoire (the VSGnome) of Trypanosoma brucei Lister 427. Mol Biochem Parasitol 195(1):59–73. doi:10.1016/j.molbiopara.2014.06.004
DeGrasse JA, DuBois KN, Devos D, Siegel TN, Sali A, Field MC, Rout MP, Chait BT (2009) Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor. Mol Cell Proteomics 8(9):2119–2130. doi:10.1074/mcp.M900038-MCP200
Deitsch KW, Lukehart SA, Stringer JR (2009) Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens. Nat Rev Microbiol 7(7):493–503. doi:10.1038/nrmicro2145
Denninger V, Fullbrook A, Bessat M, Ersfeld K, Rudenko G (2010) The FACT subunit TbSpt16 is involved in cell cycle specific control of VSG expression sites in Trypanosoma brucei. Mol Microbiol 78(2):459–474. doi:10.1111/j.1365-2958.2010.07350.x
Denninger V, Rudenko G (2014) FACT plays a major role in histone dynamics affecting VSG expression site control in Trypanosoma brucei. Mol Microbiol 94(4):945–962. doi:10.1111/mmi.12812
DiPaolo C, Kieft R, Cross M, Sabatini R (2005) Regulation of trypanosome DNA glycosylation by a SWI2/SNF2-like protein. Mol Cell 17(3):441–451. doi:10.1016/j.molcel.2004.12.022
Dooijes D, Chaves I, Kieft R, Dirks-Mulder A, Martin W, Borst P (2000) Base J originally found in kinetoplastida is also a minor constituent of nuclear DNA of Euglena gracilis. Nucleic Acids Res 28(16):3017–3021
Doyle JJ, Hirumi H, Hirumi K, Lupton EN, Cross GA (1980) Antigenic variation in clones of animal-infective Trypanosoma brucei derived and maintained in vitro. Parasitology 80(2):359–369
Dreesen O, Cross GA (2006) Consequences of telomere shortening at an active VSG expression site in telomerase-deficient Trypanosoma brucei. Eukaryot Cell 5(12):2114–2119. doi:10.1128/EC.00059-06
DuBois KN, Alsford S, Holden JM, Buisson J, Swiderski M, Bart JM, Ratushny AV, Wan Y, Bastin P, Barry JD, Navarro M, Horn D et al (2012) NUP-1 Is a large coiled-coil nucleoskeletal protein in trypanosomes with lamin-like functions. PLoS Biol 10(3):e1001287. doi:10.1371/journal.pbio.1001287
Dyer NA, Rose C, Ejeh NO, Acosta-Serrano A (2013) Flying tryps: survival and maturation of trypanosomes in tsetse flies. Trends Parasitol 29(4):188–196. doi:10.1016/j.pt.2013.02.003
Ekanayake D, Sabatini R (2011) Epigenetic regulation of polymerase II transcription initiation in Trypanosoma cruzi: modulation of nucleosome abundance, histone modification, and polymerase occupancy by O-linked thymine DNA glucosylation. Eukaryot Cell 10(11):1465–1472. doi:10.1128/EC.05185-11
Epp C, Li F, Howitt CA, Chookajorn T, Deitsch KW (2009) Chromatin associated sense and antisense noncoding RNAs are transcribed from the var gene family of virulence genes of the malaria parasite Plasmodium falciparum. RNA 15(1):116–127. doi:10.1261/rna.1080109
Ferguson MA, Homans SW, Dwek RA, Rademacher TW (1988) Glycosyl-phosphatidylinositol moiety that anchors Trypanosoma brucei variant surface glycoprotein to the membrane. Science 239(4841 Pt 1):753–759
Figueiredo LM, Cross GA (2010) Nucleosomes are depleted at the VSG expression site transcribed by RNA polymerase I in African trypanosomes. Eukaryot Cell 9(1):148–154. doi:10.1128/EC.00282-09
Figueiredo LM, Cross GA, Janzen CJ (2009) Epigenetic regulation in African trypanosomes: a new kid on the block. Nat Rev Microbiol 7(7):504–513. doi:10.1038/nrmicro2149
Figueiredo LM, Janzen CJ, Cross GA (2008) A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biol 6(7):e161. doi:10.1371/journal.pbio.0060161
Garcia-Salcedo JA, Gijon P, Nolan DP, Tebabi P, Pays E (2003) 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(21):5851–5862. doi:10.1093/emboj/cdg553
Gassen A, Brechtefeld D, Schandry N, Arteaga-Salas JM, Israel L, Imhof A, Janzen CJ (2012) DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei. Nucleic Acids Res 40(20):10302–10311. doi:10.1093/nar/gks801
Glover L, Horn D (2014) Locus-specific control of DNA resection and suppression of subtelomeric VSG recombination by HAT3 in the African trypanosome. Nucleic Acids Res 42(20):12600–12613. doi:10.1093/nar/gku900
Glover L, Hutchinson S, Alsford S, Horn D (2016) VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes. Proc Natl Acad Sci USA 113(26):7225–7230. doi:10.1073/pnas.1600344113
Gommers-Ampt JH, Van Leeuwen F, de Beer AL, Vliegenthart JF, Dizdaroglu M, Kowalak JA, Crain PF, Borst P (1993) Beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of the parasitic protozoan T. brucei. Cell 75(6):1129–1136. doi:0092-8674(93)90322-H
Gruter E, Betschart B (2001) Isolation, characterisation and organisation of histone H1 genes in African trypanosomes. Parasitol Res 87(12):977–984
Gunzl A, Bruderer T, Laufer G, Schimanski B, Tu LC, Chung HM, Lee PT, Lee MG (2003) RNA polymerase I transcribes procyclin genes and variant surface glycoprotein gene expression sites in Trypanosoma brucei. Eukaryot Cell 2(3):542–551
Hecker H, Betschart B, Bender K, Burri M, Schlimme W (1994) The chromatin of trypanosomes. Int J Parasitol 24(6):809–819. doi:0020-7519(94)90007-8
Hecker H, Gander ES (1985) The compaction pattern of the chromatin of trypanosomes. Biol Cell 53(3):199–208
Hertz-Fowler C, Figueiredo LM, Quail MA, Becker M, Jackson A, Bason N, Brooks K, Churcher C, Fahkro S, Goodhead I, Heath P, Kartvelishvili M et al (2008) Telomeric expression sites are highly conserved in Trypanosoma brucei. PloS ONE 3(10):e3527. doi:10.1371/journal.pone.0003527
Hovel-Miner GA, Boothroyd CE, Mugnier M, Dreesen O, Cross GA, Papavasiliou FN (2012) Telomere length affects the frequency and mechanism of antigenic variation in Trypanosoma brucei. PLoS Pathog 8(8):e1002900. doi:10.1371/journal.ppat.1002900
Hughes K, Wand M, Foulston L, Young R, Harley K, Terry S, Ersfeld K, Rudenko G (2007) A novel ISWI is involved in VSG expression site downregulation in African trypanosomes. EMBO J 26(9):2400–2410. doi:10.1038/sj.emboj.7601678
Ingram AK, Horn D (2002) Histone deacetylases in Trypanosoma brucei: two are essential and another is required for normal cell cycle progression. Mol Microbiol 45(1):89–97. doi:3018
Janzen CJ, Fernandez JP, Deng H, Diaz R, Hake SB, Cross GA (2006a) Unusual histone modifications in Trypanosoma brucei. FEBS Lett 580(9):2306–2310. doi:10.1016/j.febslet.2006.03.044
Janzen CJ, Hake SB, Lowell JE, Cross GA (2006b) 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(4):497–507. doi:10.1016/j.molcel.2006.06.027
Janzen CJ, Lander F, Dreesen O, Cross GA (2004) Telomere length regulation and transcriptional silencing in KU80-deficient Trypanosoma brucei. Nucleic Acids Res 32(22):6575–6584. doi:10.1093/nar/gkh991
Jehi SE, Li X, Sandhu R, Ye F, Benmerzouga I, Zhang M, Zhao Y, Li B (2014a) Suppression of subtelomeric VSG switching by Trypanosoma brucei TRF requires its TTAGGG repeat-binding activity. Nucleic Acids Res 42(20):12899–12911. doi:10.1093/nar/gku942
Jehi SE, Wu F, Li B (2014b) Trypanosoma brucei TIF2 suppresses VSG switching by maintaining subtelomere integrity. Cell Res. doi:10.1038/cr.2014.60
Kasinsky HE, Lewis JD, Dacks JB, Ausio J (2001) Origin of H1 linker histones. FASEB J 15(1):34–42. doi:10.1096/fj.00-0237rev
Kassem A, Pays E, Vanhamme L (2014) Transcription is initiated on silent variant surface glycoprotein expression sites despite monoallelic expression in Trypanosoma brucei. Proc Natl Acad Sci U S A 111(24):8943–8948. doi:10.1073/pnas.1404873111
Kawahara T, Siegel TN, Ingram AK, Alsford S, Cross GA, Horn D (2008) Two essential MYST-family proteins display distinct roles in histone H4K10 acetylation and telomeric silencing in trypanosomes. Mol Microbiol 69(4):1054–1068. doi:10.1111/j.1365-2958.2008.06346.x
Kennedy PG (2013) Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 12(2):186–194. doi:10.1016/S1474-4422(12)70296-X
Kerry LE, Pegg EE, Cameron DP, Budzak J, Poortinga G, Hannan KM, Hannan RD, Rudenko G (2017) Selective inhibition of RNA polymerase I transcription as a potential approach to treat African trypanosomiasis. PLoS Negl Trop Dis 11(3):e0005432. doi:10.1371/journal.pntd.0005432
Kim HS, Park SH, Gunzl A, Cross GA (2013) MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei. PloS one 8(2):e57001. doi:10.1371/journal.pone.0057001
Kirkham JK, Park SH, Nguyen TN, Lee JH, Gunzl A (2015) The dynein light chain LC8 is required for RNA polymerase I-mediated transcription in Trypanosoma brucei, facilitating assembly and promoter binding of class I transcription factor A. Mol Cell Biol. doi:10.1128/MCB.00705-15
Kolev NG, Franklin JB, Carmi S, Shi H, Michaeli S, Tschudi C (2010) The transcriptome of the human pathogen Trypanosoma brucei at single-nucleotide resolution. PLoS Pathog 6(9):e1001090. doi:10.1371/journal.ppat.1001090
Landeira D, Bart JM, Van Tyne D, Navarro M (2009) Cohesin regulates VSG monoallelic expression in trypanosomes. J Cell Biol 186(2):243–254. doi:10.1083/jcb.200902119
Li B, Espinal A, Cross GA (2005) Trypanosome telomeres are protected by a homologue of mammalian TRF2. Mol Cell Biol 25(12):5011–5021. doi:10.1128/MCB.25.12.5011-5021.2005
Li Z, Gourguechon S, Wang CC (2007) Tousled-like kinase in a microbial eukaryote regulates spindle assembly and S-phase progression by interacting with Aurora kinase and chromatin assembly factors. J Cell Sci 120(Pt 21):3883–3894. doi:10.1242/jcs.007955
Lopez-Farfan D, Bart JM, Rojas-Barros DI, Navarro M (2014) SUMOylation by the E3 ligase TbSIZ1/PIAS1 positively regulates VSG expression in Trypanosoma brucei. PLoS Pathog 10(12):e1004545. doi:10.1371/journal.ppat.1004545
Lowell JE, Cross GA (2004) A variant histone H3 is enriched at telomeres in Trypanosoma brucei. J Cell Sci 117(Pt 24):5937–5947. doi:10.1242/jcs.01515
Lowell JE, Kaiser F, Janzen CJ, Cross GA (2005) Histone H2AZ dimerizes with a novel variant H2B and is enriched at repetitive DNA in Trypanosoma brucei. J Cell Sci 118(Pt 24):5721–5730. doi:10.1242/jcs.02688
Mandava V, Fernandez JP, Deng H, Janzen CJ, Hake SB, Cross GA (2007) Histone modifications in Trypanosoma brucei. Mol Biochem Parasitol 156(1):41–50. doi:10.1016/j.molbiopara.2007.07.005
Maree JP, Povelones ML, Clark DJ, Rudenko G, Patterton HG (2017) Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei. Epigenetics Chromatin 10:14. doi:10.1186/s13072-017-0121-9
Matthews KR, McCulloch R, Morrison LJ (2015) The within-host dynamics of African trypanosome infections. Philos Trans R Soc Lond Ser B Biol Sci 370(1675). doi:10.1098/rstb.2014.0288
McCulloch R, Morrison LJ, Hall JP (2015) DNA recombination strategies during antigenic variation in the African Trypanosome. Microbiol Spectr 3(2). doi:10.1128/microbiolspec
Melville SE, Leech V, Navarro M, Cross GA (2000) The molecular karyotype of the megabase chromosomes of Trypanosoma brucei stock 427. Molecular and biochemical parasitology 111(2):261–273. doi:S0166685100003169
Militello KT, Wang P, Jayakar SK, Pietrasik RL, Dupont CD, Dodd K, King AM, Valenti PR (2008) African trypanosomes contain 5-methylcytosine in nuclear DNA. Eukaryot Cell 7(11):2012–2016. doi:10.1128/EC.00198-08
Mugnier MR, Cross GA, Papavasiliou FN (2015) The in vivo dynamics of antigenic variation in Trypanosoma brucei. Science 347(6229):1470–1473. doi:10.1126/science.aaa4502
Myler PJ, Allen AL, Agabian N, Stuart K (1985) Antigenic variation in clones of Trypanosoma brucei grown in immune-deficient mice. Infect Immun 47(3):684–690
Naguleswaran A, Gunasekera K, Schimanski B, Heller M, Hemphill A, Ochsenreiter T, Roditi I (2015) Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure. MBio 6(2):e00114. doi:10.1128/mBio.00114-15
Nanavaty V, Sandhu R, Jehi SE, Pandya UM, Li B (2017) Trypanosoma brucei RAP1 maintains telomere and subtelomere integrity by suppressing TERRA and telomeric RNA:DNA hybrids. Nucleic Acids Res, March 16. doi: 10.1093/nar/gkx184. [Epub ahead of print]
Narayanan MS, Kushwaha M, Ersfeld K, Fullbrook A, Stanne TM, Rudenko G (2011) NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei. Nucleic Acids Res 39(6):2018–2031. doi:10.1093/nar/gkq950
Narayanan MS, Rudenko G (2013) TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes. Nucleic Acids Res 41(5):2981–2992. doi:10.1093/nar/gks1469
Navarro M, Gull K (2001) A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414(6865):759–763. doi:10.1038/414759a
Nguyen TN, Muller LS, Park SH, Siegel TN, Gunzl A (2014) Promoter occupancy of the basal class I transcription factor A differs strongly between active and silent VSG expression sites in Trypanosoma brucei. Nucleic Acids Res 42(5):3164–3176. doi:10.1093/nar/gkt1301
Nguyen TN, Nguyen BN, Lee JH, Panigrahi AK, Gunzl A (2012) Characterization of a novel class I transcription factor A (CITFA) subunit that is indispensable for transcription by the multifunctional RNA polymerase I of Trypanosoma brucei. Eukaryot Cell 11(12):1573–1581. doi:10.1128/EC.00250-12
Pandya UM, Sandhu R, Li B (2013) Silencing subtelomeric VSGs by Trypanosoma brucei RAP1 at the insect stage involves chromatin structure changes. Nucleic Acids Res 41(16):7673–7682. doi:10.1093/nar/gkt562
Pascoalino B, Dindar G, Vieira-da-Rocha JP, Machado CR, Janzen CJ, Schenkman S (2014) Characterization of two different Asf1 histone chaperones with distinct cellular localizations and functions in Trypanosoma brucei. Nucleic Acids Res 42(5):2906–2918. doi:10.1093/nar/gkt1267
Pays E, Vanhollebeke B, Uzureau P, Lecordier L, Perez-Morga D (2014) The molecular arms race between African trypanosomes and humans. Nat Rev Microbiol 12(8):575–584. doi:10.1038/nrmicro3298
Pena AC, Pimentel MR, Manso H, Vaz-Drago R, Pinto-Neves D, Aresta-Branco F, Rijo-Ferreira F, Guegan F, Pedro Coelho L, Carmo-Fonseca M, Barbosa-Morais NL, Figueiredo LM (2014) Trypanosoma brucei histone H1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo. Mol Microbiol 93(4):645–663. doi:10.1111/mmi.12677
Povelones ML, Gluenz E, Dembek M, Gull K, Rudenko G (2012) Histone H1 plays a role in heterochromatin formation and VSG expression site silencing in Trypanosoma brucei. PLoS Pathog 8(11):e1003010. doi:10.1371/journal.ppat.1003010
Reynolds D, Cliffe L, Forstner KU, Hon CC, Siegel TN, Sabatini R (2014) Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei. Nucleic Acids Res 42(15):9717–9729. doi:10.1093/nar/gku714
Reynolds D, Hofmeister BT, Cliffe L, Alabady M, Siegel TN, Schmitz RJ, Sabatini R (2016) Histone H3 variant regulates RNA polymerase II transcription termination and dual strand transcription of siRNA loci in Trypanosoma brucei. PLoS Genet 12(1):e1005758. doi:10.1371/journal.pgen.1005758
Robinson NP, Burman N, Melville SE, Barry JD (1999) Predominance of duplicative VSG gene conversion in antigenic variation in African trypanosomes. Mol Cell Biol 19(9):5839–5846
Ross R, Thomson D (1910) A case of sleeping sickness showing regular periodical increase of the parasites disclosed. Br Med J 1(2582):1544–1545
Salmon D, Vanwalleghem G, Morias Y, Denoeud J, Krumbholz C, Lhomme F, Bachmaier S, Kador M, Gossmann J, Dias FB, De Muylder G, Uzureau P et al (2012) Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science 337(6093):463–466. doi:10.1126/science.1222753
Schlimme W, Burri M, Bender K, Betschart B, Hecker H (1993) Trypanosoma brucei brucei: differences in the nuclear chromatin of bloodstream forms and procyclic culture forms. Parasitology 107(Pt 3):237–247
Schulz D, Mugnier MR, Paulsen EM, Kim HS, Chung CW, Tough DF, Rioja I, Prinjha RK, Papavasiliou FN, Debler EW (2015) Bromodomain proteins contribute to maintenance of bloodstream form stage identity in the African trypanosome. PLoS Biol 13(12):e1002316. doi:10.1371/journal.pbio.1002316
Schulz D, Zaringhalam M, Papavasiliou FN, Kim HS (2016) Base J and H3.V regulate transcriptional termination in Trypanosoma brucei. PLoS Genet 12(1):e1005762. doi:10.1371/journal.pgen.1005762
Siegel TN, Hekstra DR, Kemp LE, Figueiredo LM, Lowell JE, Fenyo D, Wang X, Dewell S, Cross GA (2009) Four histone variants mark the boundaries of polycistronic transcription units in Trypanosoma brucei. Genes Dev 23(9):1063–1076. doi:10.1101/gad.1790409
Siegel TN, Kawahara T, Degrasse JA, Janzen CJ, Horn D, Cross GA (2008) Acetylation of histone H4K4 is cell cycle regulated and mediated by HAT3 in Trypanosoma brucei. Mol Microbiol 67(4):762–771. doi:10.1111/j.1365-2958.2007.06079.x
Stanne TM, Kushwaha M, Wand M, Taylor JE, Rudenko G (2011) TbISWI regulates multiple polymerase I (Pol I)-transcribed loci and is present at Pol II transcription boundaries in Trypanosoma brucei. Eukaryot Cell 10(7):964–976. doi:10.1128/EC.05048-11
Stanne T, Narayanan MS, Ridewood S, Ling A, Witmer K, Kushwaha M, Wiesler S, Wickstead B, Wood J, Rudenko G (2015) Identification of the ISWI chromatin remodeling complex of the early branching eukaryote Trypanosoma brucei. J Biol Chem. doi:10.1074/jbc.M115.679019
Stanne TM, Rudenko G (2010) Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes. Eukaryot Cell 9(1):136–147. doi:10.1128/EC.00281-09
Steverding D, Stierhof YD, Chaudhri M, Ligtenberg M, Schell D, Beck-Sickinger AG, Overath P (1994) ESAG 6 and 7 products of Trypanosoma brucei form a transferrin binding protein complex. Eur J Cell Biol 64(1):78–87
Thatcher TH, Gorovsky MA (1994) Phylogenetic analysis of the core histones H2A, H2B, H3, and H4. Nucleic Acids Res 22(2):174–179
Tiengwe C, Marcello L, Farr H, Dickens N, Kelly S, Swiderski M, Vaughan D, Gull K, Barry JD, Bell SD, McCulloch R (2012) Genome-wide analysis reveals extensive functional interaction between DNA replication initiation and transcription in the genome of Trypanosoma brucei. Cell Rep 2(1):185–197. doi:10.1016/j.celrep.2012.06.007
Turner CM (1997) The rate of antigenic variation in fly-transmitted and syringe-passaged infections of Trypanosoma brucei. FEMS Microbiol Lett 153(1):227–231. doi:S0378-1097(97)00266-8
Ullu E, Tschudi C (1991) Trans splicing in trypanosomes requires methylation of the 5′ end of the spliced leader RNA. Proc Natl Acad Sci U S A 88(22):10074–10078
van Leeuwen F, Taylor MC, Mondragon A, Moreau H, Gibson W, Kieft R, Borst P (1998) Beta-D-glucosyl-hydroxymethyluracil is a conserved DNA modification in kinetoplastid protozoans and is abundant in their telomeres. Proc Natl Acad Sci U S A 95(5):2366–2371
van Leeuwen F, Wijsman ER, Kieft R, van der Marel GA, van Boom JH, Borst P (1997) Localization of the modified base J in telomeric VSG gene expression sites of Trypanosoma brucei. Genes Dev 11(23):3232–3241
van Luenen HG, Farris C, Jan S, Genest PA, Tripathi P, Velds A, Kerkhoven RM, Nieuwland M, Haydock A, Ramasamy G, Vainio S, Heidebrecht T et al (2012) Glucosylated hydroxymethyluracil, DNA base J, prevents transcriptional readthrough in Leishmania. Cell 150(5):909–921. doi:10.1016/j.cell.2012.07.030
Vanhamme L, Poelvoorde P, Pays A, Tebabi P, Van Xong H, Pays E (2000) Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei. Mol Microbiol 36(2):328–340
Wang QP, Kawahara T, Horn D (2010) Histone deacetylases play distinct roles in telomeric VSG expression site silencing in African trypanosomes. Mol Microbiol 77(5):1237–1245. doi:10.1111/j.1365-2958.2010.07284.x
WHO (2015) Investing to overcome the global impact of neglected tropical diseases: third WHO report on neglected tropical diseases. Switzerland, Geneva
Wickstead B, Ersfeld K, Gull K (2004) The small chromosomes of Trypanosoma brucei involved in antigenic variation are constructed around repetitive palindromes. Genome Res 14(6):1014–1024. doi:10.1101/gr.2227704
Williams RO, Young JR, Majiwa PA (1982) Genomic environment of T. brucei VSG genes: presence of a minichromosome. Nature 299(5882):417–421
Wright JR, Siegel TN, Cross GA (2010) Histone H3 trimethylated at lysine 4 is enriched at probable transcription start sites in Trypanosoma brucei. Mol Biochem Parasitol 172(2):141–144. doi:10.1016/j.molbiopara.2010.03.013
Yang X, Figueiredo LM, Espinal A, Okubo E, Li B (2009) RAP1 is essential for silencing telomeric variant surface glycoprotein genes in Trypanosoma brucei. Cell 137(1):99–109. doi:10.1016/j.cell.2009.01.037
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Pena, A.C., Aresta-Branco, F., Figueiredo, L.M. (2017). Epigenetic Regulation in T. brucei: Changing Coats Is a Chance to Survive. In: Doerfler, W., Casadesús, J. (eds) Epigenetics of Infectious Diseases. Epigenetics and Human Health. Springer, Cham. https://doi.org/10.1007/978-3-319-55021-3_10
Download citation
DOI: https://doi.org/10.1007/978-3-319-55021-3_10
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-55019-0
Online ISBN: 978-3-319-55021-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)