LANA Binds to Multiple Active Viral and Cellular Promoters and Associates with the H3K4Methyltransferase hSET1 Complex

English version České info

KSHV is a DNA tumor virus which is associated with Kaposi's sarcoma and some lymphoproliferative diseases. During latent infection, the viral genome persists as circular extrachromosomal DNA in the nucleus and expresses a very limited number of viral proteins, including LANA, a multi-functional protein. KSHV viral episomes, like host genomic DNA, are subject to chromatin formation and histone modifications which contribute to tightly controlled gene expression during latency. We determined where LANA binds on the KSHV and human genomes, and mapped activating and repressing histone marks and RNA polymerase II binding. We found that LANA bound near transcription start sites, and binding correlated with the transcription active mark H3K4me3, but not silencing mark H3K27me3. Binding sites for transcription factors including znf143, CTCF, and Stat1 are enriched at regions where LANA is bound. We identified some LANA binding sites near human gene promoters that resembled KSHV sequences known to bind LANA. We also found a novel motif that occurs frequently in the human genome and that binds LANA directly despite being different from known LANA-binding sequences. Furthermore, we demonstrate that LANA associates with the H3K4 methyltransferase hSET1 which creates activating histone marks.

Vyšlo v časopise: LANA Binds to Multiple Active Viral and Cellular Promoters and Associates with the H3K4Methyltransferase hSET1 Complex. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004240
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004240

Souhrn

Zdroje

1. RiveraCM, RenB (2013) Mapping human epigenomes. Cell 155: 39–55.

2. BarskiA, CuddapahS, CuiK, RohTY, SchonesDE, et al. (2007) High-resolution profiling of histone methylations in the human genome. Cell 129: 823–837.

3. YuBD, HessJL, HorningSE, BrownGA, KorsmeyerSJ (1995) Altered Hox expression and segmental identity in Mll-mutant mice. Nature 378: 505–508.

4. GlaserS, MetcalfD, WuL, HartAH, DiRagoL, et al. (2006) Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia. Proc Natl Acad Sci U S A 103: 16460–16465.

5. LubitzS, GlaserS, SchaftJ, StewartAF, AnastassiadisK (2007) Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. Molecular biology of the cell 18: 2356–2366.

6. DouY, MilneTA, RuthenburgAJ, LeeS, LeeJW, et al. (2006) Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 13: 713–719.

7. StewardMM, LeeJS, O'DonovanA, WyattM, BernsteinBE, et al. (2006) Molecular regulation of H3K4 trimethylation by ASH2L, a shared subunit of MLL complexes. Nat Struct Mol Biol 13: 852–854.

8. DemersC, ChaturvediCP, RanishJA, JubanG, LaiP, et al. (2007) Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. Molecular Cell 27: 573–584.

9. RampalliS, LiL, MakE, GeK, BrandM, et al. (2007) p38 MAPK signaling regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation. Nat Struct Mol Biol 14: 1150–1156.

10. LiX, WangS, LiY, DengC, SteinerLA, et al. (2011) Chromatin boundaries require functional collaboration between the hSET1 and NURF complexes. Blood 118: 1386–1394.

11. TyagiS, ChabesAL, WysockaJ, HerrW (2007) E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Molecular Cell 27: 107–119.

12. KnipeDM, LiebermanPM, JungJU, McBrideAA, MorrisKV, et al. (2013) Snapshots: chromatin control of viral infection. Virology 435: 141–156.

13. WysockaJ, MyersMP, LahertyCD, EisenmanRN, HerrW (2003) Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes & Development 17: 896–911.

14. GrundhoffA, GanemD (2004) Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J Clin Invest 113: 124–136.

15. DittmerDP, DamaniaB (2013) Kaposi sarcoma associated herpesvirus pathogenesis (KSHV)–an update. Current opinion in virology 3: 238–244.

16. SpeckSH, GanemD (2010) Viral latency and its regulation: lessons from the gamma-herpesviruses. Cell Host Microbe 8: 100–115.

17. BallestasME, ChatisPA, KayeKM (1999) Efficient persistence of extrachromosomal KSHV DNA mediated by latency- associated nuclear antigen. Science 284: 641–644.

18. BarberaAJ, ChodaparambilJV, Kelley-ClarkeB, JoukovV, WalterJC, et al. (2006) The nucleosomal surface as a docking station for Kaposi's sarcoma herpesvirus LANA. Science 311: 856–861.

19. CotterMA2nd, RobertsonES (1999) The latency-associated nuclear antigen tethers the Kaposi's sarcoma- associated herpesvirus genome to host chromosomes in body cavity-based lymphoma cells [In Process Citation]. Virology 264: 254–264.

20. GarberAC, HuJ, RenneR (2002) Latency-associated nuclear antigen (LANA) cooperatively binds to two sites within the terminal repeat, and both sites contribute to the ability of LANA to suppress transcription and to facilitate DNA replication. J Biol Chem 277: 27401–27411.

21. HuJ, GarberAC, RenneR (2002) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus supports latent DNA replication in dividing cells. J Virol 76: 11677–11687.

22. KimKY, HuertaSB, IzumiyaC, WangDH, MartinezA, et al. (2013) Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen regulates the KSHV epigenome by association with the histone demethylase KDM3A. J Virol 87: 6782–6793.

23. SakakibaraS, UedaK, NishimuraK, DoE, OhsakiE, et al. (2004) Accumulation of heterochromatin components on the terminal repeat sequence of Kaposi's sarcoma-associated herpesvirus mediated by the latency-associated nuclear antigen. J Virol 78: 7299–7310.

24. KrithivasA, YoungDB, LiaoG, GreeneD, HaywardSD (2000) Human herpesvirus 8 LANA interacts with proteins of the mSin3 corepressor complex and negatively regulates Epstein-Barr virus gene expression in dually infected PEL cells. J Virol 74: 9637–9645.

25. LimC, GwackY, HwangS, KimS, ChoeJ (2001) The transcriptional activity of cAMP response element-binding protein- binding protein is modulated by the latency associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Biol Chem 276: 31016–31022.

26. JeongJH, OrvisJ, KimJW, McMurtreyCP, RenneR, et al. (2004) Regulation and autoregulation of the promoter for the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Biol Chem 279: 16822–16831.

27. OttingerM, ChristallaT, NathanK, BrinkmannMM, Viejo-BorbollaA, et al. (2006) Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J Virol 80: 10772–10786.

28. PlattGM, SimpsonGR, MittnachtS, SchulzTF (1999) Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the drosophila female sterile homeotic (fsh) gene [In Process Citation]. J Virol 73: 9789–9795.

29. Viejo-BorbollaA, OttingerM, BruningE, BurgerA, KonigR, et al. (2005) Brd2/RING3 interacts with a chromatin-binding domain in the Kaposi's Sarcoma-associated herpesvirus latency-associated nuclear antigen 1 (LANA-1) that is required for multiple functions of LANA-1. J Virol 79: 13618–13629.

30. LimC, LeeD, SeoT, ChoiC, ChoeJ (2003) Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus functionally interacts with heterochromatin protein 1. J Biol Chem 278: 7397–7405.

31. ShamayM, KrithivasA, ZhangJ, HaywardSD (2006) Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA. Proc Natl Acad Sci U S A 103: 14554–14559.

32. HuJ, LiuE, RenneR (2009) Involvement of SSRP1 in latent replication of Kaposi's sarcoma-associated herpesvirus. J Virol 83: 11051–11063.

33. BallestasME, KayeKM (2011) The latency-associated nuclear antigen, a multifunctional protein central to Kaposi's sarcoma-associated herpesvirus latency. Future microbiology 6: 1399–1413.

34. GuntherT, GrundhoffA The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes. PLoS Pathog 6: e1000935.

35. TothZ, MaglinteDT, LeeSH, LeeHR, WongLY, et al. (2010) Epigenetic analysis of KSHV latent and lytic genomes. PLoS pathogens 6: e1001013.

36. StedmanW, KangH, LinS, KissilJL, BartolomeiMS, et al. (2008) Cohesins localize with CTCF at the KSHV latency control region and at cellular c-myc and H19/Igf2 insulators. Embo J 27: 654–666.

37. TemperaI, LiebermanPM (2010) Chromatin organization of gammaherpesvirus latent genomes. Biochim Biophys Acta 1799: 236–245.

38. LangmeadB (2010) Aligning short sequencing reads with Bowtie. Curr Protoc Bioinformatics Chapter 11: Unit 11 17.

39. BlandJM (1986) Computer simulation of a clinical trial as an aid to teaching the concept of statistical significance. Statistics in medicine 5: 193–197.

40. BlandJM, AltmanDG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1: 307–310.

41. DudoitS, FridlyandJ (2002) A prediction-based resampling method for estimating the number of clusters in a dataset. Genome Biology 3 doi:10.1186

42. McIntyreLM, LopianoKK, MorseAM, AminV, ObergAL, et al. (2011) RNA-seq: technical variability and sampling. BMC genomics 12: 293.

43. JiH, JiangH, MaW, JohnsonDS, MyersRM, et al. (2008) An integrated software system for analyzing ChIP-chip and ChIP-seq data. Nature biotechnology 26: 1293–1300.

44. DittmerD, LagunoffM, RenneR, StaskusK, HaaseA, et al. (1998) A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus. J Virol 72: 8309–8315.

45. PearceM, MatsumuraS, WilsonAC (2005) Transcripts encoding K12, v-FLIP, v-cyclin, and the microRNA cluster of Kaposi's sarcoma-associated herpesvirus originate from a common promoter. J Virol 79: 14457–14464.

46. ChengB, LiT, RahlPB, AdamsonTE, LoudasNB, et al. (2012) Functional association of Gdown1 with RNA polymerase II poised on human genes. Molecular cell 45: 38–50.

47. FengW, LiuY, WuJ, NephewKP, HuangTH, et al. (2008) A Poisson mixture model to identify changes in RNA polymerase II binding quantity using high-throughput sequencing technology. BMC genomics 9 Suppl 2: S23.

48. GuF, HsuHK, HsuPY, WuJ, MaY, et al. (2010) Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data. BMC systems biology 4: 170.

49. DarstRP, HaeckerI, PardoCE, RenneR, KladdeMP (2013) Epigenetic diversity of Kaposi's sarcoma-associated herpesvirus. Nucleic Acids Res 41: 2993–3009.

50. ChandrianiS, GanemD (2010) Array-based transcript profiling and limiting-dilution reverse transcription-PCR analysis identify additional latent genes in Kaposi's sarcoma-associated herpesvirus. J Virol 84: 5565–5573.

51. TothZ, BruloisKF, WongLY, LeeHR, ChungB, et al. (2012) Negative elongation factor-mediated suppression of RNA polymerase II elongation of Kaposi's sarcoma-associated herpesvirus lytic gene expression. J Virol 86: 9696–9707.

52. ChenW, SinSH, WenKW, DamaniaB, DittmerDP (2012) Hsp90 inhibitors are efficacious against Kaposi Sarcoma by enhancing the degradation of the essential viral gene LANA, of the viral co-receptor EphA2 as well as other client proteins. PLoS pathogens 8: e1003048.

53. AnFQ, FolarinHM, CompitelloN, RothJ, GersonSL, et al. (2006) Long-term-infected telomerase-immortalized endothelial cells: a model for Kaposi's sarcoma-associated herpesvirus latency in vitro and in vivo. J Virol 80: 4833–4846.

54. LiebermanPM (2013) Keeping it quiet: chromatin control of gammaherpesvirus latency. Nature reviews Microbiology 11: 863–875.

55. TothZ, BruloisK, JungJU (2013) The chromatin landscape of Kaposi's sarcoma-associated herpesvirus. Viruses 5: 1346–1373.

56. HuJ, RenneR (2005) Characterization of the minimal replicator of Kaposi's sarcoma-associated herpesvirus latent origin. J Virol 79: 2637–2642.

57. RenneR, BarryC, DittmerD, CompitelloN, BrownPO, et al. (2001) Modulation of cellular and viral gene expression by the latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus. J Virol 75: 458–468.

58. LuF, TsaiK, ChenHS, WikramasingheP, DavuluriRV, et al. (2012) Identification of host-chromosome binding sites and candidate gene targets for Kaposi's sarcoma-associated herpesvirus LANA. J Virol 86: 5752–5762.

59. JeongJ, PapinJ, DittmerD (2001) Differential Regulation of the Overlapping Kaposi's Sarcoma-Associated Herpesvirus vGCR (orf74) and LANA (orf73) Promoters. J Virol 75: 1798–1807.

60. KangH, ChoH, SungGH, LiebermanPM (2013) CTCF regulates Kaposi's sarcoma-associated herpesvirus latency transcription by nucleosome displacement and RNA polymerase programming. J Virol 87: 1789–1799.

61. ChenHS, WikramasingheP, ShoweL, LiebermanPM (2012) Cohesins repress Kaposi's sarcoma-associated herpesvirus immediate early gene transcription during latency. J Virol 86: 9454–9464.

62. LanK, KuppersDA, VermaSC, SharmaN, MurakamiM, et al. (2005) Induction of Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen by the lytic transactivator RTA: a novel mechanism for establishment of latency. J Virol 79: 7453–7465.

63. LiangY, ChangJ, LynchSJ, LukacDM, GanemD (2002) The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway. Genes Dev 16: 1977–1989.

64. RossettoC, YambolievI, PariGS (2009) Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 K-bZIP modulates latency-associated nuclear protein-mediated suppression of lytic origin-dependent DNA synthesis. J Virol 83: 8492–8501.

65. BallestasME, KayeKM (2001) Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mediates episome persistence through cis-acting terminal repeat (TR) sequence and specifically binds TR DNA. J Virol 75: 3250–3258.

66. TangJ, GordonGM, MullerMG, DahiyaM, ForemanKE (2003) Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induces expression of the helix-loop-helix protein Id-1 in human endothelial cells. J Virol 77: 5975–5984.

67. LuJ, VermaSC, MurakamiM, CaiQ, KumarP, et al. (2009) Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (KSHV) upregulates survivin expression in KSHV-Associated B-lymphoma cells and contributes to their proliferation. J Virol 83: 7129–7141.

68. NojimaH, AdachiM, MatsuiT, OkawaK, TsukitaS (2008) IQGAP3 regulates cell proliferation through the Ras/ERK signalling cascade. Nature cell biology 10: 971–978.

69. Thomas-ChollierM, DarboE, HerrmannC, DefranceM, ThieffryD, et al. (2012) A complete workflow for the analysis of full-size ChIP-seq (and similar) data sets using peak-motifs. Nature protocols 7: 1551–1568.

70. Thomas-ChollierM, HerrmannC, DefranceM, SandO, ThieffryD, et al. (2012) RSAT peak-motifs: motif analysis in full-size ChIP-seq datasets. Nucleic Acids Res 40: e31.

71. BernsteinBE, BirneyE, DunhamI, GreenED, GunterC, et al. (2012) An integrated encyclopedia of DNA elements in the human genome. Nature 489: 57–74.

72. AvalleL, PensaS, RegisG, NovelliF, PoliV (2012) STAT1 and STAT3 in tumorigenesis: A matter of balance. JAK-STAT 1: 65–72.

73. JennerRG, AlbaMM, BoshoffC, KellamP (2001) Kaposi's sarcoma-associated herpesvirus latent and lytic gene expression as revealed by DNA arrays. J Virol 75: 891–902.

74. AnFQ, CompitelloN, HorwitzE, SramkoskiM, KnudsenES, et al. (2005) The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest. J Biol Chem 280: 3862–3874.

75. TothZ, BruloisK, LeeHR, IzumiyaY, TepperC, et al. (2013) Biphasic euchromatin-to-heterochromatin transition on the KSHV genome following de novo infection. PLoS pathogens 9: e1003813.

76. HiltonIB, SimonJM, LiebJD, DavisIJ, DamaniaB, et al. (2013) The Open Chromatin Landscape of Kaposi's Sarcoma-Associated Herpesvirus. J Virol 87: 11831–11842.

77. Thomas-ChollierM, DefranceM, Medina-RiveraA, SandO, HerrmannC, et al. (2011) RSAT 2011: regulatory sequence analysis tools. Nucleic Acids Res 39: W86–91.

78. Kelley-ClarkeB, De Leon-VazquezE, SlainK, BarberaAJ, KayeKM (2009) Role of Kaposi's sarcoma-associated herpesvirus C-terminal LANA chromosome binding in episome persistence. J Virol 83: 4326–4337.

79. Vazquez EdeL, CareyVJ, KayeKM (2013) Identification of Kaposi's sarcoma-associated herpesvirus LANA regions important for episome segregation, replication, and persistence. J Virol 87: 12270–12283.

80. WongLY, MatchettGA, WilsonAC (2004) Transcriptional activation by the Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen is facilitated by an N-terminal chromatin-binding motif. J Virol 78: 10074–10085.

81. MercierA, AriasC, MadridAS, HoldorfMM, GanemD (2014) Site-specific association with host and viral chromatin by KSHV LANA and its reversal during lytic replication. Journal of Virology doi: 10.1128

82. ChangHH, GanemD (2013) A unique herpesviral transcriptional program in KSHV-infected lymphatic endothelial cells leads to mTORC1 activation and rapamycin sensitivity. Cell Host & Microbe 13: 429–440.

83. YuanW, WuT, FuH, DaiC, WuH, et al. (2012) Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science 337: 971–975.

84. KrishnanHH, NaranattPP, SmithMS, ZengL, BloomerC, et al. (2004) Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression. J Virol 78: 3601–3620.

85. KangH, WiedmerA, YuanY, RobertsonE, LiebermanPM (2011) Coordination of KSHV latent and lytic gene control by CTCF-cohesin mediated chromosome conformation. PLoS Pathogens 7: e1002140.

86. LangmeadB, TrapnellC, PopM, SalzbergSL (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10: R25.

87. EdgarR, DomrachevM, LashAE (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res 30: 207–210.

88. MortazaviA, WilliamsBA, McCueK, SchaefferL, WoldB (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5: 621–628.

89. BlandJM, AltmanDG (1988) Misleading statistics: errors in textbooks, software and manuals. International Journal of Epidemiology 17: 245–247.

90. BlandJM, AltmanDJ (1986) Regression analysis. Lancet 1: 908–909.

91. LandtSG, MarinovGK, KundajeA, KheradpourP, PauliF, et al. (2012) ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia. Genome Res 22: 1813–1831.

92. RiceP, LongdenI, BleasbyA (2000) EMBOSS: the European Molecular Biology Open Software Suite. Trends in Genetics : TIG 16: 276–277.

93. QuinlanAR, HallIM (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841–842.

94. YeT, KrebsAR, ChoukrallahMA, KeimeC, PlewniakF, et al. (2011) seqMINER: an integrated ChIP-seq data interpretation platform. Nucleic Acids Res 39: e35.

95. LiY, DengC, HuX, PatelB, FuX, et al. (2012) Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis. Oncogene 31: 5007–5018.