Coordination of KSHV Latent and Lytic Gene Control by CTCF-Cohesin Mediated Chromosome Conformation

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Herpesvirus persistence requires a dynamic balance between latent and lytic cycle gene expression, but how this balance is maintained remains enigmatic. We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins. Using viral genome-wide chromatin conformation capture (3C) methods, we now show that KSHV latency control region is physically linked to the promoter regulatory region for ORF50, which encodes the KSHV immediate early protein RTA. Other linkages were also observed, including an interaction between the 5′ and 3′ end of the latency transcription cluster. Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control. siRNA depletion of CTCF or cohesin subunits also disrupted chromosomal linkages and deregulated viral latent and lytic gene transcription. Furthermore, the linkage between the latent and lytic control region was subject to cell cycle fluctuation and disrupted during lytic cycle reactivation, suggesting that these interactions are dynamic and regulatory. Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control.

Vyšlo v časopise: Coordination of KSHV Latent and Lytic Gene Control by CTCF-Cohesin Mediated Chromosome Conformation. PLoS Pathog 7(8): e32767. doi:10.1371/journal.ppat.1002140
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002140

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1. ChangYCesarmanEPessinMSLeeFCulpepperJ 1994 Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma.[comment]. Science 266 1865 1869

2. CesarmanEChangYMoorePSSaidJWKnowlesDM 1995 Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS- related body-cavity-based lymphomas [see comments]. N Engl J Med 332 1186 1191

3. SoulierJGrolletLOksenhendlerECacoubPCazals-HatemD 1995 Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86 1276 1280

4. GanemD 2006 KSHV infection and the pathogenesis of Kaposi's sarcoma. Annu Rev Pathol 1 273 296

5. SchulzTF 2006 The pleiotropic effects of Kaposi's sarcoma herpesvirus. J Pathol 208 187 198

6. WenKWDamaniaB 2010 Kaposi sarcoma-associated herpesvirus (KSHV): Molecular biology and oncogenesis. Cancer Lett 289 140 50

7. SaridRFloreOBohenzkyRAChangYMoorePS 1998 Transcription mapping of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) genome in a body cavity-based lymphoma cell line (BC-1). J Virol 72 1005 1012

8. DittmerDLagunoffMRenneRStaskusKHaaseA 1998 A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus. J Virol 72 8309 8315

9. JennerRGBoshoffC 2002 The molecular pathology of Kaposi's sarcoma-associated herpesvirus. Biochim Biophys Acta 1602 1 22

10. NadorRGMilliganLLFloreOWangXArvanitakisL 2001 Expression of Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor monocistronic and bicistronic transcripts in primary effusion lymphomas. Virology 287 62 70

11. BechtelJTLiangYHviddingJGanemD 2003 Host range of Kaposi's sarcoma-associated herpesvirus in cultured cells. J Virol 77 6474 6481

12. GuntherTGrundhoffA 2010 The epigenetic landscape of latent Kaposi sarcoma-associated herpesvirus genomes. PLoS Pathog 6 e1000935

13. LuFStedmanWYousefMRenneRLiebermanPM 2010 Epigenetic regulation of Kaposi's sarcoma-associated herpesvirus latency by virus-encoded microRNAs that target Rta and the cellular Rbl2-DNMT pathway. J Virol 84 2697 2706

14. TothZMaglinteDTLeeSHLeeHRWongLY 2010 Epigenetic analysis of KSHV latent and lytic genomes. PLoS Pathog 6 e1001013

15. StedmanWKangHLinSKissilJLBartolomeiMS 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

16. KangHLiebermanPM 2009 Cell cycle control of Kaposi's sarcoma-associated herpesvirus latency transcription by CTCF-cohesin interactions. J Virol 83 6199 6210

17. GurudattaBVCorcesVG 2009 Chromatin insulators: lessons from the fly. Brief Funct Genomic Proteomic 8 276 282

18. PhillipsJECorcesVG 2009 CTCF: master weaver of the genome. Cell 137 1194 1211

19. OhlssonRRenkawitzRLobanenkovV 2001 CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease. Trends Genet 17 520 527

20. El-KadyAKlenovaE 2005 Regulation of the transcription factor, CTCF, by phosphorylation with protein kinase CK2. FEBS Lett 579 1424 1434

21. EngelNThorvaldsenJLBartolomeiMS 2006 CTCF binding sites promote transcription initiation and prevent DNA methylation on the maternal allele at the imprinted H19/Igf2 locus. Hum Mol Genet 15 2945 2954

22. FilippovaGNLindblomAMeinckeLJKlenovaEMNeimanPE 1998 A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers. Genes Chromosomes Cancer 22 26 36

23. FilippovaGNChengMKMooreJMTruongJPHuYJ 2005 Boundaries between chromosomal domains of X inactivation and escape bind CTCF and lack CpG methylation during early development. Dev Cell 8 31 42

24. FilippovaGNThienesCPPennBHChoDHHuYJ 2001 CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus. Nat Genet 28 335 343

25. IshiharaKOshimuraMNakaoM 2006 CTCF-dependent chromatin insulator is linked to epigenetic remodeling. Mol Cell 23 733 742

26. LingJQLiTHuJFVuTHChenHL 2006 CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science 312 269 272

27. YusufzaiTMTagamiHNakataniYFelsenfeldG 2004 CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell 13 291 298

28. OhlssonRLobanenkovVKlenovaE 2010 Does CTCF mediate between nuclear organization and gene expression? Bioessays 32 37 50

29. GasznerMFelsenfeldG 2006 Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 7 703 713

30. BarskiACuddapahSCuiKRohTYSchonesDE 2007 High-resolution profiling of histone methylations in the human genome. Cell 129 823 837

31. CuddapahSJothiRSchonesDERohTYCuiK 2009 Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19 24 32

32. RubioEDReissDJWelcshPLDistecheCMFilippovaGN 2008 CTCF physically links cohesin to chromatin. Proc Natl Acad Sci U S A 105 8309 8314

33. WendtKSYoshidaKItohTBandoMKochB 2008 Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451 796 801

34. FuYSinhaMPetersonCLWengZ 2008 The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome. PLoS Genet 4 e1000138

35. HaeringCHFarcasAMArumugamPMetsonJNasmythK 2008 The cohesin ring concatenates sister DNA molecules. Nature 454 297 301

36. NasmythKHaeringCH 2005 The structure and function of SMC and kleisin complexes. Annu Rev Biochem 74 595 648

37. DorsettD 2007 Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes. Chromosoma 116 1 13

38. BoseTGertonJL 2010 Cohesinopathies, gene expression, and chromatin organization. J Cell Biol 189 201 210

39. KrantzIDMcCallumJDeScipioCKaurMGillisLA 2004 Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B. Nat Genet 36 631 635

40. KageyMHNewmanJJBilodeauSZhanYOrlandoDA 2010 Mediator and cohesin connect gene expression and chromatin architecture. Nature 467 430 435

41. DekkerJ 2006 The three ‘C’ s of chromosome conformation capture: controls, controls, controls. Nat Methods 3 17 21

42. DekkerJRippeKDekkerMKlecknerN 2002 Capturing chromosome conformation. Science 295 1306 1311

43. ZhaoZTavoosidanaGSjolinderMGondorAMarianoP 2006 Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions. Nat Genet 38 1341 1347

44. DostieJRichmondTAArnaoutRASelzerRRLeeWL 2006 Chromosome Conformation Capture Carbon Copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16 1299 1309

45. LuFDayLGaoSJLiebermanPM 2006 Acetylation of the latency-associated nuclear antigen regulates repression of Kaposi's sarcoma-associated herpesvirus lytic transcription. J Virol 80 5273 5282

46. BellarePGanemD 2009 Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe 6 570 575

47. LeiXBaiZYeFXieJKimCG 2010 Regulation of NF-kappaB inhibitor IkappaBalpha and viral replication by a KSHV microRNA. Nat Cell Biol 12 193 199

48. LanKKuppersDAVermaSCRobertsonES 2004 Kaposi's sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen inhibits lytic replication by targeting Rta: a potential mechanism for virus-mediated control of latency. J Virol 78 6585 6594

49. MatsumuraSFujitaYGomezETaneseNWilsonAC 2005 Activation of the Kaposi's sarcoma-associated herpesvirus major latency locus by the lytic switch protein RTA (ORF50). J Virol 79 8493 8505

50. GrundhoffAGanemD 2004 Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J Clin Invest 113 124 136

51. SplinterEHeathHKoorenJPalstraRJKlousP 2006 CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev 20 2349 2354

52. LanKKuppersDARobertsonES 2005 Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway. J Virol 79 3468 3478

53. PetersJMTedeschiASchmitzJ 2008 The cohesin complex and its roles in chromosome biology. Genes Dev 22 3089 3114

54. LemanARNoguchiCLeeCYNoguchiE 2010 Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion. J Cell Sci 123 660 670

55. BernsteinBEMikkelsenTSXieXKamalMHuebertDJ 2006 A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 315 326

56. Kheradmand KiaSSolaimani KartalaeiPFarahbakhshianEPourfarzadFvon LindernM 2009 EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence. Epigenetics Chromatin 2 16

57. LiTHuJFQiuXLingJChenH 2008 CTCF regulates allelic expression of Igf2 by orchestrating a promoter-polycomb repressive complex 2 intrachromosomal loop. Mol Cell Biol 28 6473 6482

58. TiwariVKMcGarveyKMLicchesiJDOhmJEHermanJG 2008 PcG proteins, DNA methylation, and gene repression by chromatin looping. PLoS Biol 6 2911 2927

59. VassetzkyYGavrilovAEivazovaEPriozhkovaILipinskiM 2009 Chromosome conformation capture (from 3C to 5C) and its ChIP-based modification. Methods Mol Biol 567 171 188