Suicidal Autointegration of and Transposons in Eukaryotic Cells

English version České info

Transposons (“jumping genes”) are ubiquitous, mobile genetic elements that make up significant fraction of genomes, and are best described as molecular parasites. During ‘cut and paste’ transposition, the excised transposon relocates from one genomic location to another. Here we focus on the molecular events following excision of two eukaryotic DNA transposons, Sleeping Beauty and piggyBac. Both transposons are primarily used in a cellular environment that is different from their original hosts, thereby offering a new model to study host-parasite interaction in higher organisms. In the last decade, they have been developed into a technology platform for vertebrate genetics, including gene discovery, transgenesis, gene therapy and stem cell manipulation. Despite the wide range of their application, relatively little is known about their molecular mechanism in vertebrates. We show that these elements are not capable of self-avoidance, as a significant portion of the excised transposons integrates into its own genome in a suicidal process. Despite mechanistic differences, both transposons are affected similarly, and larger transposons are particularly vulnerable. We propose that transposons might recruit phylogenetically conserved cellular factors in a new host that protects against self-disruption. Suboptimal conditions in a new environment could generate abnormal, genotoxic transposition reactions, and should be monitored.

Vyšlo v časopise: Suicidal Autointegration of and Transposons in Eukaryotic Cells. PLoS Genet 10(3): e32767. doi:10.1371/journal.pgen.1004103
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004103

Souhrn

Zdroje

1. CraigNL (1995) Unity in transposition reactions. Science 270: 253–254.

2. GueguenE, RousseauP, Duval-ValentinG, ChandlerM (2005) The transpososome: control of transposition at the level of catalysis. Trends Microbiol 13: 543–549.

3. AgrenJA, WrightSI (2011) Co-evolution between transposable elements and their hosts: a major factor in genome size evolution? Chromosome Res 19: 777–786.

4. LeungPC, TeplowDB, HarsheyRM (1989) Interaction of distinct domains in Mu transposase with Mu DNA ends and an internal transpositional enhancer. Nature 338: 656–658.

5. KettingRF, HaverkampTH, van LuenenHG, PlasterkRH (1999) Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99: 133–141.

6. TabaraH, SarkissianM, KellyWG, FleenorJ, GrishokA, et al. (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99: 123–132.

7. ChalmersR, GuhathakurtaA, BenjaminH, KlecknerN (1998) IHF modulation of Tn10 transposition: sensory transduction of supercoiling status via a proposed protein/DNA molecular spring. Cell 93: 897–908.

8. Claeys BouuaertC, LipkowK, AndrewsSS, LiuD, ChalmersR (2013) The autoregulation of a eukaryotic DNA transposon. Elife 2: e00668.

9. IvicsZ, HackettPB, PlasterkRH, IzsvakZ (1997) Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 91: 501–510.

10. IzsvakZ, StuweEE, FiedlerD, KatzerA, JeggoPA, et al. (2004) Healing the wounds inflicted by sleeping beauty transposition by double-strand break repair in mammalian somatic cells. Mol Cell 13: 279–290.

11. ZayedH, IzsvakZ, KhareD, HeinemannU, IvicsZ (2003) The DNA-bending protein HMGB1 is a cellular cofactor of Sleeping Beauty transposition. Nucleic Acids Res 31: 2313–2322.

12. WaliskoO, IzsvakZ, SzaboK, KaufmanCD, HeroldS, et al. (2006) Sleeping Beauty transposase modulates cell-cycle progression through interaction with Miz-1. Proc Natl Acad Sci U S A 103: 4062–4067.

13. WaliskoO, SchornA, RolfsF, DevarajA, MiskeyC, et al. (2008) Transcriptional activities of the Sleeping Beauty transposon and shielding its genetic cargo with insulators. Mol Ther 16: 359–369.

14. ChiangSJ, JordanE, ClowesRC (1982) Intermolecular and intramolecular transposition and transposition immunity in Tn3 and Tn2660. Mol Gen Genet 187: 187–194.

15. BenjaminHW, KlecknerN (1989) Intramolecular transposition by Tn10. Cell 59: 373–383.

16. TomcsanyiT, BergCM, PhadnisSH, BergDE (1990) Intramolecular transposition by a synthetic IS50 (Tn5) derivative. J Bacteriol 172: 6348–6354.

17. SignonL, KlecknerN (1995) Negative and positive regulation of Tn10/IS10-promoted recombination by IHF: two distinguishable processes inhibit transposition off of multicopy plasmid replicons and activate chromosomal events that favor evolution of new transposons. Genes Dev 9: 1123–1136.

18. WardleSJ, O'CarrollM, DerbyshireKM, HanifordDB (2005) The global regulator H-NS acts directly on the transpososome to promote Tn10 transposition. Genes Dev 19: 2224–2235.

19. SinghRK, LiburdJ, WardleSJ, HanifordDB (2008) The nucleoid binding protein H-NS acts as an anti-channeling factor to favor intermolecular Tn10 transposition and dissemination. J Mol Biol 376: 950–962.

20. HanifordDB (2006) Transpososome dynamics and regulation in Tn10 transposition. Crit Rev Biochem Mol Biol 41: 407–424.

21. Claeys BouuaertC, ChalmersR (2010) Transposition of the human Hsmar1 transposon: rate-limiting steps and the importance of the flanking TA dinucleotide in second strand cleavage. Nucleic Acids Res 38: 190–202.

22. SinzelleL, JegotG, BrilletB, Rouleux-BonninF, BigotY, et al. (2008) Factors acting on Mos1 transposition efficiency. BMC Mol Biol 9: 106.

23. LeeMS, CraigieR (1998) A previously unidentified host protein protects retroviral DNA from autointegration. Proc Natl Acad Sci U S A 95: 1528–1533.

24. LiY, KappesJC, ConwayJA, PriceRW, ShawGM, et al. (1991) Molecular characterization of human immunodeficiency virus type 1 cloned directly from uncultured human brain tissue: identification of replication-competent and -defective viral genomes. J Virol 65: 3973–3985.

25. GarfinkelDJ, StefaniskoKM, NyswanerKM, MooreSP, OhJ, et al. (2006) Retrotransposon suicide: formation of Ty1 circles and autointegration via a central DNA flap. J Virol 80: 11920–11934.

26. KlecknerN, ChalmersRM, KwonD, SakaiJ, BollandS (1996) Tn10 and IS10 transposition and chromosome rearrangements: mechanism and regulation in vivo and in vitro. Curr Top Microbiol Immunol 204: 49–82.

27. GreenblattIM (1984) A Chromosome Replication Pattern Deduced from Pericarp Phenotypes Resulting from Movements of the Transposable Element, Modulator, in Maize. Genetics 108: 471–485.

28. HorieK, YusaK, YaeK, OdajimaJ, FischerSE, et al. (2003) Characterization of Sleeping Beauty transposition and its application to genetic screening in mice. Mol Cell Biol 23: 9189–9207.

29. IzsvakZ, IvicsZ, PlasterkRH (2000) Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. J Mol Biol 302: 93–102.

30. KarsiA, MoavB, HackettP, LiuZ (2001) Effects of insert size on transposition efficiency of the sleeping beauty transposon in mouse cells. Mar Biotechnol (NY) 3: 241–245.

31. FraserMJ, SmithGE, SummersMD (1983) Acquisition of Host Cell DNA Sequences by Baculoviruses: Relationship Between Host DNA Insertions and FP Mutants of Autographa californica and Galleria mellonella Nuclear Polyhedrosis Viruses. J Virol 47: 287–300.

32. LuoG, IvicsZ, IzsvakZ, BradleyA (1998) Chromosomal transposition of a Tc1/mariner-like element in mouse embryonic stem cells. Proc Natl Acad Sci U S A 95: 10769–10773.

33. MitraR, Fain-ThorntonJ, CraigNL (2008) piggyBac can bypass DNA synthesis during cut and paste transposition. EMBO J 27: 1097–1109.

34. LoboNF, FraserTS, AdamsJA, FraserMJJr (2006) Interplasmid transposition demonstrates piggyBac mobility in vertebrate species. Genetica 128: 347–357.

35. HozumiA, MitaK, MiskeyC, MatesL, IzsvakZ, et al. (2013) Germline transgenesis of the chordate Ciona intestinalis with hyperactive variants of sleeping beauty transposable element. Dev Dyn 242: 30–43.

36. WangW, BradleyA, HuangY (2009) A piggyBac transposon-based genome-wide library of insertionally mutated Blm-deficient murine ES cells. Genome Res 19: 667–673.

37. RostovskayaM, FuJ, ObstM, BaerI, WeidlichS, et al. (2012) Transposon-mediated BAC transgenesis in human ES cells. Nucleic Acids Res 40: e150.

38. KimH, KimK, KimJ, KimSH, YimJ (2012) Mutagenesis by imprecise excision of the piggyBac transposon in Drosophila melanogaster. Biochem Biophys Res Commun 417: 335–339.

39. KengVW, YaeK, HayakawaT, MizunoS, UnoY, et al. (2005) Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system. Nat Methods 2: 763–769.

40. WangW, LinC, LuD, NingZ, CoxT, et al. (2008) Chromosomal transposition of PiggyBac in mouse embryonic stem cells. Proc Natl Acad Sci U S A 105: 9290–9295.

41. DingS, WuX, LiG, HanM, ZhuangY, et al. (2005) Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice. Cell 122: 473–483.

42. IvicsZ, LiMA, MatesL, BoekeJD, NagyA, et al. (2009) Transposon-mediated genome manipulation in vertebrates. Nat Methods 6: 415–422.

43. NairJ, RouseDA, BaiGH, MorrisSL (1993) The rpsL gene and streptomycin resistance in single and multiple drug-resistant strains of Mycobacterium tuberculosis. Mol Microbiol 10: 521–527.

44. MatesL, ChuahMK, BelayE, JerchowB, ManojN, et al. (2009) Molecular evolution of a novel hyperactive Sleeping Beauty transposase enables robust stable gene transfer in vertebrates. Nat Genet 41: 753–61.

45. VigdalTJ, KaufmanCD, IzsvakZ, VoytasDF, IvicsZ (2002) Common physical properties of DNA affecting target site selection of sleeping beauty and other Tc1/mariner transposable elements. J Mol Biol 323: 441–452.

46. YantSR, WuX, HuangY, GarrisonB, BurgessSM, et al. (2005) High-resolution genome-wide mapping of transposon integration in mammals. Mol Cell Biol 25: 2085–2094.

47. AmmarI, Gogol-DoringA, MiskeyC, ChenW, CathomenT, et al. (2012) Retargeting transposon insertions by the adeno-associated virus Rep protein. Nucleic Acids Res 40 (14) 6693–712.

48. GeurtsAM, HackettCS, BellJB, BergemannTL, CollierLS, et al. (2006) Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res 34: 2803–2811.

49. FraserMJ, BruscaJS, SmithGE, SummersMD (1985) Transposon-mediated mutagenesis of a baculovirus. Virology 145: 356–361.

50. CadinanosJ, BradleyA (2007) Generation of an inducible and optimized piggyBac transposon system. Nucleic Acids Res 35: e87.

51. EnglishJJ, HarrisonK, JonesJ (1995) Aberrant Transpositions of Maize Double Ds-Like Elements Usually Involve Ds Ends on Sister Chromatids. Plant Cell 7: 1235–1247.

52. IzsvakZ, KhareD, BehlkeJ, HeinemannU, PlasterkRH, et al. (2002) Involvement of a bifunctional, paired-like DNA-binding domain and a transpositional enhancer in Sleeping Beauty transposition. J Biol Chem 277: 34581–34588.

53. FischerSE, van LuenenHG, PlasterkRH (1999) Cis requirements for transposition of Tc1-like transposons in C. elegans. Mol Gen Genet 262: 268–274.

54. LampeDJ, GrantTE, RobertsonHM (1998) Factors affecting transposition of the Himar1 mariner transposon in vitro. Genetics 149: 179–187.

55. UrasakiA, MorvanG, KawakamiK (2006) Functional dissection of the Tol2 transposable element identified the minimal cis-sequence and a highly repetitive sequence in the subterminal region essential for transposition. Genetics 174: 639–649.

56. IbrahimN, WicklundA, WiebeMS (2011) Molecular characterization of the host defense activity of the barrier to autointegration factor against vaccinia virus. J Virol 85: 11588–11600.

57. UmlandTC, WeiSQ, CraigieR, DaviesDR (2000) Structural basis of DNA bridging by barrier-to-autointegration factor. Biochemistry 39: 9130–9138.

58. BradleyCM, RonningDR, GhirlandoR, CraigieR, DydaF (2005) Structural basis for DNA bridging by barrier-to-autointegration factor. Nat Struct Mol Biol 12: 935–936.

59. TangD, KangR, ZehHJ3rd, LotzeMT (2010) High-mobility group box 1 and cancer. Biochim Biophys Acta 1799: 131–140.

60. CalogeroS, GrassiF, AguzziA, VoigtlanderT, FerrierP, et al. (1999) The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice. Nat Genet 22: 276–280.

61. VermeulenM, HubnerNC, MannM (2008) High confidence determination of specific protein-protein interactions using quantitative mass spectrometry. Curr Opin Biotechnol 19: 331–337.

62. MansharamaniM, GrahamDR, MonieD, LeeKK, HildrethJE, et al. (2003) Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is a host component of human immunodeficiency virus type 1 virions. J Virol 77: 13084–13092.

63. StellwagenAE, CraigNL (1997) Avoiding self: two Tn7-encoded proteins mediate target immunity in Tn7 transposition. EMBO J 16: 6823–6834.

64. AdzumaK, MizuuchiK (1989) Interaction of proteins located at a distance along DNA: mechanism of target immunity in the Mu DNA strand-transfer reaction. Cell 57: 41–47.

65. CaiM, HuangY, GhirlandoR, WilsonKL, CraigieR, et al. (2001) Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. Embo J 20: 4399–4407.

66. MargalitA, BrachnerA, GotzmannJ, FoisnerR, GruenbaumY (2007) Barrier-to-autointegration factor–a BAFfling little protein. Trends Cell Biol 17: 202–208.

67. WiebeMS, TraktmanP (2007) Poxviral B1 kinase overcomes barrier to autointegration factor, a host defense against virus replication. Cell Host Microbe 1: 187–197.

68. LeeMS, CraigieR (1994) Protection of retroviral DNA from autointegration: involvement of a cellular factor. Proc Natl Acad Sci U S A 91: 9823–9827.

69. SuzukiY, CraigieR (2002) Regulatory mechanisms by which barrier-to-autointegration factor blocks autointegration and stimulates intermolecular integration of Moloney murine leukemia virus preintegration complexes. J Virol 76: 12376–12380.

70. WhitfieldCR, WardleSJ, HanifordDB (2009) The global bacterial regulator H-NS promotes transpososome formation and transposition in the Tn5 system. Nucleic Acids Res 37: 309–321.

71. WaliskoO, SchornA, RolfsF, DevarajA, MiskeyC, et al. (2007) Transcriptional Activities of the Sleeping Beauty Transposon and Shielding Its Genetic Cargo With Insulators. Mol Ther

72. GrabundzijaI, IrgangM, MatesL, BelayE, MatraiJ, et al. (2010) Comparative analysis of transposable element vector systems in human cells. Mol Ther 18: 1200–1209.

73. LiMA, TurnerDJ, NingZ, YusaK, LiangQ, et al. (2011) Mobilization of giant piggyBac transposons in the mouse genome. Nucleic Acids Res 39: e148.

74. LiangQ, KongJ, StalkerJ, BradleyA (2009) Chromosomal mobilization and reintegration of Sleeping Beauty and PiggyBac transposons. Genesis 47: 404–408.

75. HuangJT, DoonerHK (2012) The spectrum and frequency of self-inflicted and host gene mutations produced by the transposon Ac in maize. Plant Cell 24: 4149–4162.

76. HuetF, LuJT, MyrickKV, BaughLR, CrosbyMA, et al. (2002) A deletion-generator compound element allows deletion saturation analysis for genomewide phenotypic annotation. Proc Natl Acad Sci U S A 99: 9948–9953.

77. PrestonCR, SvedJA, EngelsWR (1996) Flanking duplications and deletions associated with P-induced male recombination in Drosophila. Genetics 144: 1623–1638.

78. PageDR, KohlerC, Da Costa-NunesJA, BarouxC, MooreJM, et al. (2004) Intrachromosomal excision of a hybrid Ds element induces large genomic deletions in Arabidopsis. Proc Natl Acad Sci U S A 101: 2969–2974.

79. MartinC, MackayS, CarpenterR (1988) Large-Scale Chromosomal Restructuring Is Induced by the Transposable Element Tam3 at the Nivea Locus of Antirrhinum Majus. Genetics 119: 171–184.

80. AvilaP, GrinstedJ, de la CruzF (1988) Analysis of the variable endpoints generated by one-ended transposition of Tn21. J Bacteriol 170: 1350–1353.

81. GrayYH (2000) It takes two transposons to tango: transposable-element-mediated chromosomal rearrangements. Trends Genet 16: 461–468.

82. StadtfeldM, HochedlingerK (2009) Without a trace? PiggyBac-ing toward pluripotency. Nat Methods 6: 329–330.

83. DaviesDR, GoryshinIY, ReznikoffWS, RaymentI (2000) Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 289: 77–85.

84. Claeys BouuaertC, LiuD, ChalmersR (2011) A simple topological filter in a eukaryotic transposon as a mechanism to suppress genome instability. Mol Cell Biol 31: 317–327.

85. van GentDC, HiomK, PaullTT, GellertM (1997) Stimulation of V(D)J cleavage by high mobility group proteins. EMBO J 16: 2665–2670.

86. AgrawalA, SchatzDG (1997) RAG1 and RAG2 form a stable postcleavage synaptic complex with DNA containing signal ends in V(D)J recombination. Cell 89: 43–53.

87. GeurtsAM, YangY, ClarkKJ, LiuG, CuiZ, et al. (2003) Gene transfer into genomes of human cells by the sleeping beauty transposon system. Mol Ther 8: 108–117.

88. KaufmanCD, IzsvakZ, KatzerA, IvicsZ (2005) Frog Prince transposon-based RNAi vectors mediate efficient gene knockdown in human cells. J RNAi Gene Silencing 1: 97–104.

89. CoxJ, MannM (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26: 1367–1372.