A Shared Role for RBF1 and dCAP-D3 in the Regulation of Transcription with Consequences for Innate Immunity

English version České info

Previously, we discovered a conserved interaction between RB proteins and the Condensin II protein CAP-D3 that is important for ensuring uniform chromatin condensation during mitotic prophase. The Drosophila melanogaster homologs RBF1 and dCAP-D3 co-localize on non-dividing polytene chromatin, suggesting the existence of a shared, non-mitotic role for these two proteins. Here, we show that the absence of RBF1 and dCAP-D3 alters the expression of many of the same genes in larvae and adult flies. Strikingly, most of the genes affected by the loss of RBF1 and dCAP-D3 are not classic cell cycle genes but are developmentally regulated genes with tissue-specific functions and these genes tend to be located in gene clusters. Our data reveal that RBF1 and dCAP-D3 are needed in fat body cells to activate transcription of clusters of antimicrobial peptide (AMP) genes. AMPs are important for innate immunity, and loss of either dCAP-D3 or RBF1 regulation results in a decrease in the ability to clear bacteria. Interestingly, in the adult fat body, RBF1 and dCAP-D3 bind to regions flanking an AMP gene cluster both prior to and following bacterial infection. These results describe a novel, non-mitotic role for the RBF1 and dCAP-D3 proteins in activation of the Drosophila immune system and suggest dCAP-D3 has an important role at specific subsets of RBF1-dependent genes.

Vyšlo v časopise: A Shared Role for RBF1 and dCAP-D3 in the Regulation of Transcription with Consequences for Innate Immunity. PLoS Genet 8(4): e32767. doi:10.1371/journal.pgen.1002618
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002618

Souhrn

Zdroje

1. HanahanDWeinbergRA 2000 The hallmarks of cancer. Cell 100 57 70

2. SherrCJMcCormickF 2002 The RB and p53 pathways in cancer. Cancer Cell 2 103 112

3. TrimarchiJMLeesJA 2002 Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3 11 20

4. ThomasDMCartySAPiscopoDMLeeJSWangWF 2001 The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol Cell 8 303 316

5. SchneiderJGuWZhuLMahdaviVNadal-GinardB 1994 Reversal of terminal differentiation mediated by p107 in Rb-/- muscle cells 10.1126/science.8197461. Science 264 1467 1471

6. NovitchBMulliganGJacksTLassarA 1996 Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G2 phases of the cell cycle 10.1083/jcb.135.2.441. J Cell Biol 135 441 456

7. ZacksenhausEJiangZChungDMarthJDPhillipsRA 1996 pRb controls proliferation, differentiation, and death of skeletal muscle cells and other lineages during embryogenesis. Genes Dev 10 3051 3064

8. NicolayBNBayarmagnaiBMoonNSBenevolenskayaEVFrolovMV 2010 Combined inactivation of pRB and hippo pathways induces dedifferentiation in the Drosophila retina. PLoS Genet 6 e1000918 doi:10.1371/journal.pgen.1000918

9. LongworthMSDysonNJ 2010 pRb, a local chromatin organizer with global possibilities. Chromosoma 119 1 11

10. IsaacCEFrancisSMMartensALJulianLMSeifriedLA 2006 The retinoblastoma protein regulates pericentric heterochromatin. Mol Cell Biol 26 3659 3671

11. LongworthMSHerrAJiJYDysonNJ 2008 RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3. Genes Dev 22 1011 1024

12. ManningALLongworthMSDysonNJ 2010 Loss of pRB causes centromere dysfunction and chromosomal instability. Genes Dev 24 1364 1376

13. GerlichDHirotaTKochBPetersJMEllenbergJ 2006 Condensin I stabilizes chromosomes mechanically through a dynamic interaction in live cells. Curr Biol 16 333 344

14. OnoTLosadaAHiranoMMyersMPNeuwaldAF 2003 Differential contributions of condensin I and condensin II to mitotic chromosome architecture in vertebrate cells. Cell 115 109 121

15. SteffensenSCoelhoPACobbeNVassSCostaM 2001 A role for Drosophila SMC4 in the resolution of sister chromatids in mitosis. Curr Biol 11 295 307

16. HirotaTGerlichDKochBEllenbergJPetersJM 2004 Distinct functions of condensin I and II in mitotic chromosome assembly. J Cell Sci 117 6435 6445

17. Bazett-JonesDPKimuraKHiranoT 2002 Efficient supercoiling of DNA by a single condensin complex as revealed by electron spectroscopic imaging. Mol Cell 9 1183 1190

18. StrickTRKawaguchiTHiranoT 2004 Real-time detection of single-molecule DNA compaction by condensin I. Curr Biol 14 874 880

19. OnoTFangYSpectorDLHiranoT 2004 Spatial and temporal regulation of Condensins I and II in mitotic chromosome assembly in human cells. Mol Biol Cell 15 3296 3308

20. KimuraKCuvierOHiranoT 2001 Chromosome condensation by a human condensin complex in Xenopus egg extracts. J Biol Chem 276 5417 5420

21. GoslingKMMakaroffLETheodoratosAKimYHWhittleB 2007 A mutation in a chromosome condensin II subunit, kleisin beta, specifically disrupts T cell development. Proc Natl Acad Sci U S A 104 12445 12450

22. XuYLeungCGLeeDCKennedyBKCrispinoJD 2006 MTB, the murine homolog of condensin II subunit CAP-G2, represses transcription and promotes erythroid cell differentiation. Leukemia 20 1261 1269

23. CobbeNSavvidouEHeckMM 2006 Diverse mitotic and interphase functions of condensins in Drosophila. Genetics 172 991 1008

24. DejKJAhnCOrr-WeaverTL 2004 Mutations in the Drosophila condensin subunit dCAP-G: defining the role of condensin for chromosome condensation in mitosis and gene expression in interphase. Genetics 168 895 906

25. LemaitreBHoffmannJ 2007 The host defense of Drosophila melanogaster. Annu Rev Immunol 25 697 743

26. DimovaDKStevauxOFrolovMVDysonNJ 2003 Cell cycle-dependent and cell cycle-independent control of transcription by the Drosophila E2F/RB pathway. Genes Dev 17 2308 2320

27. KwonSYXiaoHGloverBPTjianRWuC 2008 The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila innate immunity. Dev Biol 316 538 547

28. MeisterM 2004 Blood cells of Drosophila: cell lineages and role in host defence. Curr Opin Immunol 16 10 15

29. KuruczEMarkusRZsambokiJFolkl-MedzihradszkyKDarulaZ 2007 Nimrod, a putative phagocytosis receptor with EGF repeats in Drosophila plasmatocytes. Curr Biol 17 649 654

30. LebestkyTChangTHartensteinVBanerjeeU 2000 Specification of Drosophila hematopoietic lineage by conserved transcription factors. Science 288 146 149

31. AlfonsoTBJonesBW 2002 gcm2 promotes glial cell differentiation and is required with glial cells missing for macrophage development in Drosophila. Dev Biol 248 369 383

32. LanotRZacharyDHolderFMeisterM 2001 Postembryonic hematopoiesis in Drosophila. Dev Biol 230 243 257

33. Elrod-EricksonMMishraSSchneiderD 2000 Interactions between the cellular and humoral immune responses in Drosophila. Curr Biol 10 781 784

34. NappiAJOttavianiE 2000 Cytotoxicity and cytotoxic molecules in invertebrates. Bioessays 22 469 480

35. IrvingPUbedaJMDoucetDTroxlerLLagueuxM 2005 New insights into Drosophila larval haemocyte functions through genome-wide analysis. Cell Microbiol 7 335 350

36. WertheimBKraaijeveldARSchusterEBlancEHopkinsM 2005 Genome-wide gene expression in response to parasitoid attack in Drosophila. Genome Biol 6 R94

37. UvellHEngstromY 2007 A multilayered defense against infection: combinatorial control of insect immune genes. Trends Genet 23 342 349

38. BrennanCAAndersonKV 2004 Drosophila: the genetics of innate immune recognition and response. Annu Rev Immunol 22 457 483

39. ImlerJLBuletP 2005 Antimicrobial peptides in Drosophila: structures, activities and gene regulation. Chem Immunol Allergy 86 1 21

40. DiAngeloJRBirnbaumMJ 2009 Regulation of fat cell mass by insulin in Drosophila melanogaster. Mol Cell Biol 29 6341 6352

41. AggarwalKSilvermanN 2008 Positive and negative regulation of the Drosophila immune response. BMB Rep 41 267 277

42. FerrandonDImlerJLHetruCHoffmannJA 2007 The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nat Rev Immunol 7 862 874

43. SengerKHarrisKLevineM 2006 GATA factors participate in tissue-specific immune responses in Drosophila larvae. Proc Natl Acad Sci U S A 103 15957 15962

44. TanjiTYunEYIpYT 2010 Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proc Natl Acad Sci U S A 107 14715 14720

45. MeisterMBraunAKapplerCReichhartJMHoffmannJA 1994 Insect immunity. A transgenic analysis in Drosophila defines several functional domains in the diptericin promoter. Embo J 13 5958 5966

46. GeorgelPMeisterMKapplerCLemaitreBReichhartJM 1993 Insect immunity: the diptericin promoter contains multiple functional regulatory sequences homologous to mammalian acute-phase response elements. Biochem Biophys Res Commun 197 508 517

47. KapplerCMeisterMLagueuxMGateffEHoffmannJA 1993 Insect immunity. Two 17 bp repeats nesting a kappa B-related sequence confer inducibility to the diptericin gene and bind a polypeptide in bacteria-challenged Drosophila. Embo J 12 1561 1568

48. ValanneSMyllymakiHKallioJSchmidMRKleinoA 2010 Genome-wide RNA interference in Drosophila cells identifies G protein-coupled receptor kinase 2 as a conserved regulator of NF-kappaB signaling. J Immunol 184 6188 6198

49. MengXKhanujaBSIpYT 1999 Toll receptor-mediated Drosophila immune response requires Dif, an NF-kappaB factor. Genes Dev 13 792 797

50. KanekoTSilvermanN 2005 Bacterial recognition and signalling by the Drosophila IMD pathway. Cell Microbiol 7 461 469

51. KocksCChoJHNehmeNUlvilaJPearsonAM 2005 Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila. Cell 123 335 346

52. AyresJSFreitagNSchneiderDS 2008 Identification of Drosophila mutants altering defense of and endurance to Listeria monocytogenes infection. Genetics 178 1807 1815

53. AyresJSSchneiderDS 2008 A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections. PLoS Biol 6 e305 doi:10.1371/journal.pbio.0060305

54. DionneMSPhamLNShirasu-HizaMSchneiderDS 2006 Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Curr Biol 16 1977 1985

55. SchneiderDSAyresJS 2008 Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol 8 889 895

56. KorenjakMTaylor-HardingBBinneUKSatterleeJSStevauxO 2004 Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes. Cell 119 181 193

57. LewisPWBeallELFleischerTCGeorletteDLinkAJ 2004 Identification of a Drosophila Myb-E2F2/RBF transcriptional repressor complex. Genes Dev 18 2929 2940

58. DiamondGBeckloffNWeinbergAKisichKO 2009 The roles of antimicrobial peptides in innate host defense. Curr Pharm Des 15 2377 2392

59. KimuraKHiranoT 2000 Dual roles of the 11S regulatory subcomplex in condensin functions. Proc Natl Acad Sci U S A 97 11972 11977

60. HartlTASmithHFBoscoG 2008 Chromosome alignment and transvection are antagonized by condensin II. Science 322 1384 1387

61. PetersenUMKadalayilLRehornKPHoshizakiDKReuterR 1999 Serpent regulates Drosophila immunity genes in the larval fat body through an essential GATA motif. Embo J 18 4013 4022

62. HiranoT 2006 At the heart of the chromosome: SMC proteins in action. Nat Rev Mol Cell Biol 7 311 322

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

64. HiranoT 2005 SMC proteins and chromosome mechanics: from bacteria to humans. Philos Trans R Soc Lond B Biol Sci 360 507 514

65. NativioRWendtKSItoYHuddlestonJEUribe-LewisS 2009 Cohesin is required for higher-order chromatin conformation at the imprinted IGF2-H19 locus. PLoS Genet 5 e1000739 doi:10.1371/journal.pgen.1000739

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

67. FerrandonDJungACCriquiMLemaitreBUttenweiler-JosephS 1998 A drosomycin-GFP reporter transgene reveals a local immune response in Drosophila that is not dependent on the Toll pathway. Embo J 17 1217 1227

68. RyuJHNamKBOhCTNamHJKimSH 2004 The homeobox gene Caudal regulates constitutive local expression of antimicrobial peptide genes in Drosophila epithelia. Mol Cell Biol 24 172 185

69. TzouPOhresserSFerrandonDCapovillaMReichhartJM 2000 Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia. Immunity 13 737 748

70. KimMLeeJHLeeSYKimEChungJ 2006 Caspar, a suppressor of antibacterial immunity in Drosophila. Proc Natl Acad Sci U S A 103 16358 16363

71. RyuJHKimSHLeeHYBaiJYNamYD 2008 Innate immune homeostasis by the homeobox gene caudal and commensal-gut mutualism in Drosophila. Science 319 777 782

72. GobertVGottarMMatskevichAARutschmannSRoyetJ 2003 Dual activation of the Drosophila toll pathway by two pattern recognition receptors. Science 302 2126 2130

73. Pili-FlourySLeulierFTakahashiKSaigoKSamainE 2004 In vivo RNA interference analysis reveals an unexpected role for GNBP1 in the defense against Gram-positive bacterial infection in Drosophila adults. J Biol Chem 279 12848 12853

74. BergmanPJohanssonLAspVPlantLGudmundssonGH 2005 Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide LL-37. Cell Microbiol 7 1009 1017

75. ChakrabortyKGhoshSKoleyHMukhopadhyayAKRamamurthyT 2008 Bacterial exotoxins downregulate cathelicidin (hCAP-18/LL-37) and human beta-defensin 1 (HBD-1) expression in the intestinal epithelial cells. Cell Microbiol 10 2520 2537

76. SperandioBRegnaultBGuoJZhangZStanleySLJr 2008 Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression. J Exp Med 205 1121 1132

77. WehkampJSalzmanNHPorterENudingSWeichenthalM 2005 Reduced Paneth cell alpha-defensins in ileal Crohn's disease. Proc Natl Acad Sci U S A 102 18129 18134

78. MarkeyMPBergseidJBoscoEEStengelKXuH 2007 Loss of the retinoblastoma tumor suppressor: differential action on transcriptional programs related to cell cycle control and immune function. Oncogene 26 6307 6318

79. ZurawskiDVMumyKLFahertyCSMcCormickBAMaurelliAT 2009 Shigella flexneri type III secretion system effectors OspB and OspF target the nucleus to downregulate the host inflammatory response via interactions with retinoblastoma protein. Mol Microbiol 71 350 368

80. TsichritzisTGaentzschPCKosmidisSBrownAESkoulakisEM 2007 A Drosophila ortholog of the human cylindromatosis tumor suppressor gene regulates triglyceride content and antibacterial defense. Development 134 2605 2614

81. BolstadBMIrizarryRAAstrandMSpeedTP 2003 A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19 185 193

82. SmythGK 2004 Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3 Article3

83. BenjaminiYHochbergY 1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society Series 57 289 300

84. TweedieSAshburnerMFallsKLeylandPMcQuiltonP 2009 FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Res 37 D555 559

85. RomeoYLemaitreB 2008 Drosophila immunity: methods for monitoring the activity of Toll and Imd signaling pathways. Methods Mol Biol 415 379 394