SUMOylation by the E3 Ligase TbSIZ1/PIAS1 Positively Regulates VSG Expression in
African trypanosomes have evolved one of the most complex strategies of immune evasion by routinely switching the expression of surface proteins called Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Previous work has suggested that the recruitment of a single VSG telomeric locus to a discrete nuclear body (ESB) underlies the mechanism responsible for VSG monoallelic expression. Our findings establish unexpected roles for SUMOylation as a specific post-translational modification that marks the ESB and the VSG-ES chromatin. We describe a highly SUMOylated focus (HSF) as a novel nuclear structure that partially colocalizes with the VSG-ES locus and the nuclear body ESB. Furthermore, chromatin SUMOylation is a distinct feature of the active VSG-ES locus, in contrast to other loci investigated. SUMOylation of chromatin-associated proteins is required for efficient recruitment of the polymerase to the VSG-ES promoter and for VSG-ES expression. Altogether, these data suggest the presence of a large number of SUMOylated proteins associated with monoallelic expression as Protein Group SUMOylation. In contrast to the wealth of literature focused on VSG regulation by silencing, our results indicate a positive mechanism via SUMOylation to regulate VSG expression in the infectious form of this protozoan parasite.
Vyšlo v časopise:
SUMOylation by the E3 Ligase TbSIZ1/PIAS1 Positively Regulates VSG Expression in. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004545
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004545
Souhrn
African trypanosomes have evolved one of the most complex strategies of immune evasion by routinely switching the expression of surface proteins called Variant Surface Glycoproteins (VSG), only one of which is expressed at any given time. Previous work has suggested that the recruitment of a single VSG telomeric locus to a discrete nuclear body (ESB) underlies the mechanism responsible for VSG monoallelic expression. Our findings establish unexpected roles for SUMOylation as a specific post-translational modification that marks the ESB and the VSG-ES chromatin. We describe a highly SUMOylated focus (HSF) as a novel nuclear structure that partially colocalizes with the VSG-ES locus and the nuclear body ESB. Furthermore, chromatin SUMOylation is a distinct feature of the active VSG-ES locus, in contrast to other loci investigated. SUMOylation of chromatin-associated proteins is required for efficient recruitment of the polymerase to the VSG-ES promoter and for VSG-ES expression. Altogether, these data suggest the presence of a large number of SUMOylated proteins associated with monoallelic expression as Protein Group SUMOylation. In contrast to the wealth of literature focused on VSG regulation by silencing, our results indicate a positive mechanism via SUMOylation to regulate VSG expression in the infectious form of this protozoan parasite.
Zdroje
1. McCullochR (2004) Antigenic variation in African trypanosomes: monitoring progress. Trends Parasitol 20: 117–121.
2. PaysE, VanhammeL, Perez-MorgaD (2004) Antigenic variation in Trypanosoma brucei: facts, challenges and mysteries. Curr Opin Microbiol 7: 369–374.
3. Hertz-FowlerC, FigueiredoLM, QuailMA, BeckerM, JacksonA, et al. (2008) Telomeric expression sites are highly conserved in Trypanosoma brucei. PLoS ONE 3: e3527.
4. NavarroM, GullK (2001) A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei. Nature 414: 759–763.
5. BorstP (2002) Antigenic variation and allelic exclusion. Cell 109: 5–8.
6. GloverL, HutchinsonS, AlsfordS, McCullochR, FieldMC, et al. (2013) Antigenic variation in African trypanosomes: the importance of chromosomal and nuclear context in VSG expression control. Cell Microbiol 15: 1984–1993.
7. StanneTM, KushwahaM, WandM, TaylorJE, RudenkoG (2011) TbISWI regulates multiple polymerase I (Pol I)-transcribed loci and is present at Pol II transcription boundaries in Trypanosoma brucei. Eukaryot Cell 10: 964–976.
8. YangX, FigueiredoLM, EspinalA, OkuboE, LiB (2009) RAP1 is essential for silencing telomeric variant surface glycoprotein genes in Trypanosoma brucei. Cell 137: 99–109.
9. FigueiredoLM, JanzenCJ, CrossGA (2008) A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biol 6: e161.
10. DenningerV, FullbrookA, BessatM, ErsfeldK, RudenkoG (2010) The FACT subunit TbSpt16 is involved in cell cycle specific control of VSG expression sites in Trypanosoma brucei. Mol Microbiol 78: 459–474.
11. FigueiredoLM, CrossGA (2010) Nucleosomes are depleted at the VSG expression site transcribed by RNA polymerase I in African trypanosomes. Eukaryot Cell 9: 148–154.
12. StanneTM, RudenkoG (2010) Active VSG expression sites in Trypanosoma brucei are depleted of nucleosomes. Eukaryot Cell 9: 136–147.
13. NarayananMS, RudenkoG (2013) TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes. Nucleic Acids Res 41: 2981–2992.
14. PenateX, Lopez-FarfanD, LandeiraD, WentlandA, VidalI, et al. (2009) RNA pol II subunit RPB7 is required for RNA pol I-mediated transcription in Trypanosoma brucei. EMBO Rep 10: 252–257.
15. ParkSH, NguyenTN, KirkhamJK, LeeJH, GunzlA (2011) Transcription by the multifunctional RNA polymerase I in Trypanosoma brucei functions independently of RPB7. Mol Biochem Parasitol
16. NavarroM, PenateX, LandeiraD, Lopez-FarfanD (2011) Role of RPB7 in RNA pol I transcription in Trypanosoma brucei. Mol Biochem Parasitol 180: 43–44.
17. MatunisMJ, CoutavasE, BlobelG (1996) A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex. J Cell Biol 135: 1457–1470.
18. MahajanR, DelphinC, GuanT, GeraceL, MelchiorF (1997) A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2. Cell 88: 97–107.
19. GareauJR, LimaCD (2010) The SUMO pathway: emerging mechanisms that shape specificity, conjugation and recognition. Nat Rev Mol Cell Biol 11: 861–871.
20. JohnsonES (2004) Protein modification by SUMO. Annu Rev Biochem 73: 355–382.
21. JohnsonES, GuptaAA (2001) An E3-like factor that promotes SUMO conjugation to the yeast septins. Cell 106: 735–744.
22. TozluogluM, KaracaE, NussinovR, HalilogluT (2010) A mechanistic view of the role of E3 in sumoylation. PLoS Comput Biol 6.
23. SchmidtD, MullerS (2003) PIAS/SUMO: new partners in transcriptional regulation. Cell Mol Life Sci 60: 2561–2574.
24. ZhaoX, BlobelG (2005) A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A 102: 4777–4782.
25. LeeMH, LeeSW, LeeEJ, ChoiSJ, ChungSS, et al. (2006) SUMO-specific protease SUSP4 positively regulates p53 by promoting Mdm2 self-ubiquitination. Nat Cell Biol 8: 1424–1431.
26. KirshO, SeelerJS, PichlerA, GastA, MullerS, et al. (2002) The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase. EMBO J 21: 2682–2691.
27. KageyMH, MelhuishTA, WottonD (2003) The polycomb protein Pc2 is a SUMO E3. Cell 113: 127–137.
28. LystMJ, StanchevaI (2007) A role for SUMO modification in transcriptional repression and activation. Biochem Soc Trans 35: 1389–1392.
29. LiaoS, WangT, FanK, TuX (2010) The small ubiquitin-like modifier (SUMO) is essential in cell cycle regulation in Trypanosoma brucei. Exp Cell Res 316: 704–715.
30. ObadoSO, BotC, EcheverryMC, BayonaJC, AlvarezVE, et al. (2011) Centromere-associated topoisomerase activity in bloodstream form Trypanosoma brucei. Nucleic Acids Res 39: 1023–1033.
31. BayonaJC, NakayasuES, LaverriereM, AguilarC, SobreiraTJ, et al. (2011) SUMOylation pathway in Trypanosoma cruzi: functional characterization and proteomic analysis of target proteins. Mol Cell Proteomics 10: M110 007369.
32. KleinCA, DrollD, ClaytonC (2013) SUMOylation in Trypanosoma brucei. PeerJ 1: e180.
33. BeckerJ, BaryschSV, KaracaS, DittnerC, HsiaoHH, et al. (2013) Detecting endogenous SUMO targets in mammalian cells and tissues. Nat Struct Mol Biol 20: 525–531.
34. LandeiraD, BartJM, Van TyneD, NavarroM (2009) Cohesin regulates VSG monoallelic expression in trypanosomes. J Cell Biol 186: 243–254.
35. LandeiraD, NavarroM (2007) Nuclear repositioning of the VSG promoter during developmental silencing in Trypanosoma brucei. J Cell Biol 176: 133–139.
36. LiuHW, ZhangJ, HeineGF, AroraM, Gulcin OzerH, et al. (2012) Chromatin modification by SUMO-1 stimulates the promoters of translation machinery genes. Nucleic Acids Res 40: 10172–10186.
37. RosoninaE, DuncanSM, ManleyJL (2010) SUMO functions in constitutive transcription and during activation of inducible genes in yeast. Genes Dev 24: 1242–1252.
38. MelchiorF, SchergautM, PichlerA (2003) SUMO: ligases, isopeptidases and nuclear pores. Trends Biochem Sci 28: 612–618.
39. Alm-KristiansenAH, LorenzoPI, MolvaersmyrAK, MatreV, LedsaakM, et al. (2011) PIAS1 interacts with FLASH and enhances its co-activation of c-Myb. Mol Cancer 10: 21.
40. XhemalceB, SeelerJS, ThonG, DejeanA, ArcangioliB (2004) Role of the fission yeast SUMO E3 ligase Pli1p in centromere and telomere maintenance. Embo J 23: 3844–3853.
41. PsakhyeI, JentschS (2012) Protein group modification and synergy in the SUMO pathway as exemplified in DNA repair. Cell 151: 807–820.
42. WohlschlegelJA, JohnsonES, ReedSI, YatesJR3rd (2004) Global analysis of protein sumoylation in Saccharomyces cerevisiae. J Biol Chem 279: 45662–45668.
43. MaoYS, ZhangB, SpectorDL (2011) Biogenesis and function of nuclear bodies. Trends Genet 27: 295–306.
44. NavarroM, PenateX, LandeiraD (2007) Nuclear architecture underlying gene expression in Trypanosoma brucei. Trends Microbiol 15: 263–270.
45. Cubenas-PottsC, MatunisMJ (2013) SUMO: a multifaceted modifier of chromatin structure and function. Dev Cell 24: 1–12.
46. Garcia-DominguezM, ReyesJC (2009) SUMO association with repressor complexes, emerging routes for transcriptional control. Biochim Biophys Acta 1789: 451–459.
47. NathanD, IngvarsdottirK, SternerDE, BylebylGR, DokmanovicM, et al. (2006) Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev 20: 966–976.
48. ShiioY, EisenmanRN (2003) Histone sumoylation is associated with transcriptional repression. Proc Natl Acad Sci U S A 100: 13225–13230.
49. SharrocksAD (2006) PIAS proteins and transcriptional regulation–more than just SUMO E3 ligases? Genes Dev 20: 754–758.
50. AlbuquerqueCP, WangG, LeeNS, KolodnerRD, PutnamCD, et al. (2013) Distinct SUMO ligases cooperate with Esc2 and Slx5 to suppress duplication-mediated genome rearrangements. PLoS Genet 9: e1003670.
51. FlothoA, MelchiorF (2013) Sumoylation: a regulatory protein modification in health and disease. Annu Rev Biochem 82: 357–385.
52. TakahashiY, DulevS, LiuX, HillerNJ, ZhaoX, et al. (2008) Cooperation of sumoylated chromosomal proteins in rDNA maintenance. PLoS Genet 4: e1000215.
53. KassemA, PaysE, VanhammeL (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: 8943–8948.
54. AlmedawarS, ColominaN, Bermudez-LopezM, Pocino-MerinoI, Torres-RosellJ (2012) A SUMO-dependent step during establishment of sister chromatid cohesion. Curr Biol 22: 1576–1581.
55. FigueiredoLM, CrossGA, JanzenCJ (2009) Epigenetic regulation in African trypanosomes: a new kid on the block. Nat Rev Microbiol 7: 504–513.
56. HeunP (2007) SUMOrganization of the nucleus. Curr Opin Cell Biol 19: 350–355.
57. GuizettiJ, ScherfA (2013) Silence, activate, poise and switch! Mechanisms of antigenic variation in Plasmodium falciparum. Cell Microbiol 15: 718–726.
58. PruccaCG, LujanHD (2009) Antigenic variation in Giardia lamblia. Cell Microbiol 11: 1706–1715.
59. WirtzE, LealS, OchattC, CrossGA (1999) A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei. Mol Biochem Parasitol 99: 89–101.
60. LowellJE, CrossGA (2004) A variant histone H3 is enriched at telomeres in Trypanosoma brucei. J Cell Sci 117: 5937–5947.
61. WangZ, MorrisJC, DrewME, EnglundPT (2000) Inhibition of Trypanosoma brucei gene expression by RNA interference using an integratable vector with opposing T7 promoters. J Biol Chem 275: 40174–40179.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
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