Nuclear domain 10-associated proteins recognize and segregate intranuclear DNA/protein complexes to negate gene expression

Virology Journal

Qiyi Tang¹  Bruno R Rojas¹  Yisel A Rivera-Molina¹ 

[1] Department of Microbiology/RCMI Program, Ponce School of Medicine and Health Sciences, Ponce, 00716, Puerto Rico

关键词: Nuclear bodies;    Transcript location;    Daxx;    PML;    Lac repressor;    Lac operator;    Amplicon;    Protein-DNA complexes;    Nuclear domain 10 (ND10);   

Others  :  1153646
DOI  :  10.1186/1743-422X-9-222

 received in 2012-07-10, accepted in 2012-09-27,  发布年份 2012

【 摘 要 】

Background

DNA viruses, such as herpes simplex virus type 1 (HSV-1), Simian virus 40 (SV40), and Cytomegaloviruses (CMV), start their replicative processes and transcription at specific nuclear domains known as ND10 (nuclear domain 10, also called PML bodies). It has been previously determined that for HSV-1 and SV40, a short DNA sequence and its binding protein are required and sufficient for cell localization of viral DNA replication and gene transcription.

Results

Our recent observations provide evidence that a foreign (not endogenous) DNA/protein complex in the nucleus recruits ND10 proteins. First, the complexes formed from the bacterial lac operator DNA and its binding protein (lac repressor), or from HPV11 (human papillomavirus 11) origin DNA and its binding protein (E2), co-localized with different ND10 proteins. Second, the HSV-1 amplicon without inserted lac operator DNA repeats distributed in the nucleus randomly, whereas the amplicon with lac operator DNA repeats associated with ND10, suggesting that DNA-binding proteins are required to localize at ND10. The cellular intrinsic DNA/protein complex (as detected for U2 DNA) showed no association with ND10. Furthermore, our examination of PML−/−, Daxx−/−, and Sp100-negative cells led to our discovering that DNA/protein complexes recruit ND10 protein independently. Using the GFP-LacI/Operator system, we were able to direct the transfected DNA to ND10 and found that gene expression was significantly repressed when the transfected DNA was directed to ND10.

Conclusion

Taken together, the results suggest that cells recognize DNA/protein complexes through a mechanism that involves interaction with the ND10-associated proteins.

【 授权许可】

   
2012 Rivera-Molina et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Misteli T: Where the nucleus comes from. Trends Cell Biol 2001, 11:149.
• [2]Dundr M, Misteli T: Biogenesis of nuclear bodies. Cold Spring Harb Perspect Biol 2010, 2:a000711.
• [3]Zhao R, Bodnar MS, Spector DL: Nuclear neighborhoods and gene expression. Curr Opin Genet Dev 2009, 19:172-179.
• [4]Lamond AI, Earnshaw WC: Structure and function in the nucleus. Science 1998, 280:547-553.
• [5]Spector DL: SnapShot: cellular bodies. Cell 2006, 127:1071.
• [6]Dundr M, Misteli T: Functional architecture in the cell nucleus. Biochem J 2001, 356:297-310.
• [7]Trotman LC, Mosberger N, Fornerod M, Stidwill RP, Greber UF: Import of adenovirus DNA involves the nuclear pore complex receptor CAN/Nup214 and histone H1. Nat Cell Biol 2001, 3:1092-1100.
• [8]Ishov AM, Maul GG: The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition. J Cell Biol 1996, 134:815-826.
• [9]Maul GG, Ishov AM, Everett RD: Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1. Virology 1996, 217:67-75.
• [10]Tang Q, Li L, Ishov AM, Revol V, Epstein AL, Maul GG: Determination of minimum herpes simplex virus type 1 components necessary to localize transcriptionally active DNA to ND10. J Virol 2003, 77:5821-5828.
• [11]Tang Q, Maul GG: Mouse cytomegalovirus immediate-early protein 1 binds with host cell repressors to relieve suppressive effects on viral transcription and replication during lytic infection. J Virol 2003, 77:1357-1367.
• [12]Tavalai N, Stamminger T: New insights into the role of the subnuclear structure ND10 for viral infection. Biochim Biophys Acta 2008, 1783:2207-2221.
• [13]Tavalai N, Papior P, Rechter S, Leis M, Stamminger T: Evidence for a role of the cellular ND10 protein PML in mediating intrinsic immunity against human cytomegalovirus infections. J Virol 2006, 80:8006-8018.
• [14]Roberts S, Hillman ML, Knight GL, Gallimore PH: The ND10 component promyelocytic leukemia protein relocates to human papillomavirus type 1 E4 intranuclear inclusion bodies in cultured keratinocytes and in warts. J Virol 2003, 77:673-684.
• [15]Negorev DG, Vladimirova OV, Maul GG: Differential functions of interferon-upregulated Sp100 isoforms: herpes simplex virus type 1 promoter-based immediate-early gene suppression and PML protection from ICP0-mediated degradation. J Virol 2009, 83:5168-5180.
• [16]Ling PD, Peng RS, Nakajima A, Yu JH, Tan J, Moses SM, Yang WH, Zhao B, Kieff E, Bloch KD, Bloch DB: Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100. EMBO J 2005, 24:3565-3575.
• [17]Gu H, Roizman B: The degradation of promyelocytic leukemia and Sp100 proteins by herpes simplex virus 1 is mediated by the ubiquitin-conjugating enzyme UbcH5a. Proc Natl Acad Sci U S A 2003, 100:8963-8968.
• [18]Puvion-Dutilleul F, Venturini L, Guillemin MC, de The H, Puvion E: Sequestration of PML and Sp100 proteins in an intranuclear viral structure during herpes simplex virus type 1 infection. Exp Cell Res 1995, 221:448-461.
• [19]Chelbi-Alix MK, de The H: Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene 1999, 18:935-941.
• [20]Saffert RT, Kalejta RF: Human cytomegalovirus gene expression is silenced by Daxx-mediated intrinsic immune defense in model latent infections established in vitro. J Virol 2007, 81:9109-9120.
• [21]Woodhall DL, Groves IJ, Reeves MB, Wilkinson G, Sinclair JH: Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem 2006, 281:37652-37660.
• [22]Saffert RT, Kalejta RF: Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp 71 protein stimulates viral immediate-early gene expression. J Virol 2006, 80:3863-3871.
• [23]Hofmann H, Sindre H, Stamminger T: Functional interaction between the pp 71 protein of human cytomegalovirus and the PML-interacting protein human Daxx. J Virol 2002, 76:5769-5783.
• [24]Maul GG, Guldner HH, Spivack JG: Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol 1993, 74(Pt 12):2679-2690.
• [25]Everett RD, Maul GG: HSV-1 IE protein Vmw110 causes redistribution of PML. EMBO J 1994, 13:5062-5069.
• [26]Korioth F, Maul GG, Plachter B, Stamminger T, Frey J: The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp Cell Res 1996, 229:155-158.
• [27]Mocarski ES, Kemble GW, Lyle JM, Greaves RF: A deletion mutant in the human cytomegalovirus gene encoding IE1(491aa) is replication defective due to a failure in autoregulation. Proc Natl Acad Sci U S A 1996, 93:11321-11326.
• [28]Stow ND, Stow EC: Isolation and characterization of a herpes simplex virus type 1 mutant containing a deletion within the gene encoding the immediate early polypeptide Vmw110. J Gen Virol 1986, 67(Pt 12):2571-2585.
• [29]Maul GG: Nuclear domain 10, the site of DNA virus transcription and replication. Bioessays 1998, 20:660-667.
• [30]Tang Q, Bell P, Tegtmeyer P, Maul GG: Replication but not transcription of simian virus 40 DNA is dependent on nuclear domain 10. J Virol 2000, 74:9694-9700.
• [31]Everett RD, Murray J: ND10 components relocate to sites associated with herpes simplex virus type 1 nucleoprotein complexes during virus infection. J Virol 2005, 79:5078-5089.
• [32]Cuchet-Lourenco D, Boutell C, Lukashchuk V, Grant K, Sykes A, Murray J, Orr A, Everett RD: SUMO pathway dependent recruitment of cellular repressors to herpes simplex virus type 1 genomes. PLoS Pathog 2011, 7:e1002123.
• [33]Robinett CC, Straight A, Li G, Willhelm C, Sudlow G, Murray A, Belmont AS: In vivo localization of DNA sequences and visualization of large-scale chromatin organization using lac operator/repressor recognition. J Cell Biol 1996, 135:1685-1700.
• [34]Belmont AS, Li G, Sudlow G, Robinett C: Visualization of large-scale chromatin structure and dynamics using the lac operator/lac repressor reporter system. Methods Cell Biol 1999, 58:203-222.
• [35]Belmont AS, Straight AF: In vivo visualization of chromosomes using lac operator-repressor binding. Trends Cell Biol 1998, 8:121-124.
• [36]Muratani M, Gerlich D, Janicki SM, Gebhard M, Eils R, Spector DL: Metabolic-energy-dependent movement of PML bodies within the mammalian cell nucleus. Nat Cell Biol 2002, 4:106-110.
• [37]Tsukamoto T, Hashiguchi N, Janicki SM, Tumbar T, Belmont AS, Spector DL: Visualization of gene activity in living cells. Nat Cell Biol 2000, 2:871-878.
• [38]Smith KP, Carter KC, Johnson CV, Lawrence JB: U2 and U1 snRNA gene loci associate with coiled bodies. J Cell Biochem 1995, 59:473-485.
• [39]Kurz A, Lampel S, Nickolenko JE, Bradl J, Benner A, Zirbel RM, Cremer T, Lichter P: Active and inactive genes localize preferentially in the periphery of chromosome territories. J Cell Biol 1996, 135:1195-1205.
• [40]Plehn-Dujowich D, Bell P, Ishov AM, Baumann C, Maul GG: Non-apoptotic chromosome condensation induced by stress: delineation of interchromosomal spaces. Chromosoma 2000, 109:266-279.
• [41]Xing Y, Johnson CV, Moen PT Jr, McNeil JA, Lawrence J: Nonrandom gene organization: structural arrangements of specific pre-mRNA transcription and splicing with SC-35 domains. J Cell Biol 1995, 131:1635-1647.
• [42]Lorenz P, Baker BF, Bennett CF, Spector DL: Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies. Mol Biol Cell 1998, 9:1007-1023.
• [43]Fanti L, Dorer DR, Berloco M, Henikoff S, Pimpinelli S: Heterochromatin protein 1 binds transgene arrays. Chromosoma 1998, 107:286-292.
• [44]Ishov AM, Sotnikov AG, Negorev D, Vladimirova OV, Neff N, Kamitani T, Yeh ET, Strauss JF 3rd, Maul GG: PML is critical for ND10 formation and recruits the PML-interacting protein daxx to this nuclear structure when modified by SUMO-1. J Cell Biol 1999, 147:221-234.
• [45]Kiriakidou M, Driscoll DA, Lopez-Guisa JM, 3rd Strauss JF: Cloning and expression of primate Daxx cDNAs and mapping of the human gene to chromosome 6p21.3 in the MHC region. DNA Cell Biol 1997, 16:1289-1298.
• [46]Ishov AM, Vladimirova OV, Maul GG: Heterochromatin and ND10 are cell-cycle regulated and phosphorylation-dependent alternate nuclear sites of the transcription repressor Daxx and SWI/SNF protein ATRX. J Cell Sci 2004, 117:3807-3820.
• [47]Ahn JH, Jang WJ, Hayward GS: The human cytomegalovirus IE2 and UL112-113 proteins accumulate in viral DNA replication compartments that initiate from the periphery of promyelocytic leukemia protein-associated nuclear bodies (PODs or ND10). J Virol 1999, 73:10458-10471.
• [48]Ishov AM, Stenberg RM, Maul GG: Human cytomegalovirus immediate early interaction with host nuclear structures: definition of an immediate transcript environment. J Cell Biol 1997, 138:5-16.
• [49]Maul GG: Initiation of cytomegalovirus infection at ND10. Curr Top Microbiol Immunol 2008, 325:117-132.
• [50]Everett RD, Chelbi-Alix MK: PML and PML nuclear bodies: implications in antiviral defence. Biochimie 2007, 89:819-830.
• [51]Lehembre F, Muller S, Pandolfi PP, Dejean A: Regulation of Pax3 transcriptional activity by SUMO-1-modified PML. Oncogene 2001, 20:1-9.
• [52]Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD: Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol Cell Biol 2000, 20:1784-1796.
• [53]Mu ZM, Chin KV, Liu JH, Lozano G, Chang KS: PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol 1994, 14:6858-6867.
• [54]Seeler JS, Marchio A, Sitterlin D, Transy C, Dejean A: Interaction of SP100 with HP1 proteins: a link between the promyelocytic leukemia-associated nuclear bodies and the chromatin compartment. Proc Natl Acad Sci U S A 1998, 95:7316-7321.
• [55]Vallian S, Chin KV, Chang KS: The promyelocytic leukemia protein interacts with Sp1 and inhibits its transactivation of the epidermal growth factor receptor promoter. Mol Cell Biol 1998, 18:7147-7156.
• [56]Wasylyk C, Schlumberger SE, Criqui-Filipe P, Wasylyk B: Sp100 interacts with ETS-1 and stimulates its transcriptional activity. Mol Cell Biol 2002, 22:2687-2702.
• [57]Burkham J, Coen DM, Weller SK: ND10 protein PML is recruited to herpes simplex virus type 1 prereplicative sites and replication compartments in the presence of viral DNA polymerase. J Virol 1998, 72:10100-10107.
• [58]Lukonis CJ, Weller SK: Formation of herpes simplex virus type 1 replication compartments by transfection: requirements and localization to nuclear domain 10. J Virol 1997, 71:2390-2399.
• [59]Boisvert FM, Hendzel MJ, Bazett-Jones DP: Promyelocytic leukemia (PML) nuclear bodies are protein structures that do not accumulate RNA. J Cell Biol 2000, 148:283-292.
• [60]Shiels C, Islam SA, Vatcheva R, Sasieni P, Sternberg MJ, Freemont PS, Sheer D: PML bodies associate specifically with the MHC gene cluster in interphase nuclei. J Cell Sci 2001, 114:3705-3716.
• [61]Sotnikov AG, Negorev D, Ishov AM, Maul GG: [Monoclonal antibodies against protein Daxx and its localization in nuclear domains 10]. Tsitologiia 2001, 43:1123-1129.
• [62]Maul GG, Yu E, Ishov AM, Epstein AL: Nuclear domain 10 (ND10) associated proteins are also present in nuclear bodies and redistribute to hundreds of nuclear sites after stress. J Cell Biochem 1995, 59:498-513.
• [63]Kretz-Remy C, Tanguay RM: SUMO/sentrin: protein modifiers regulating important cellular functions. Biochem Cell Biol 1999, 77:299-309.
• [64]Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ 3rd: SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins. Genes Dev 2002, 16:919-932.
• [65]Ascoli CA, Maul GG: Identification of a novel nuclear domain. J Cell Biol 1991, 112:785-795.
• [66]Jegou T, Chung I, Heuvelman G, Wachsmuth M, Gorisch SM, Greulich-Bode KM, Boukamp P, Lichter P, Rippe K: Dynamics of telomeres and promyelocytic leukemia nuclear bodies in a telomerase-negative human cell line. Mol Biol Cell 2009, 20:2070-2082.
• [67]Logvinoff C, Epstein AL: Genetic engineering of herpes simplex virus and vector genomes carrying loxP sites in cells expressing Cre recombinase. Virology 2000, 267:102-110.
• [68]Logvinoff C, Epstein AL: A novel approach for herpes simplex virus type 1 amplicon vector production, using the Cre-loxP recombination system to remove helper virus. Hum Gene Ther 2001, 12:161-167.
• [69]Dao LD, Duffy A, Van Tine BA, Wu SY, Chiang CM, Broker TR, Chow LT: Dynamic localization of the human papillomavirus type 11 origin binding protein E2 through mitosis while in association with the spindle apparatus. J Virol 2006, 80:4792-4800.
• [70]Pavelitz T, Rusche L, Matera AG, Scharf JM, Weiner AM: Concerted evolution of the tandem array encoding primate U2 snRNA occurs in situ, without changing the cytological context of the RNU2 locus. EMBO J 1995, 14:169-177.
• [71]Lindgren V, Luskey KL, Russell DW, Francke U: Human genes involved in cholesterol metabolism: chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. Proc Natl Acad Sci U S A 1985, 82:8567-8571.
• [72]Bolla MK, Miller GJ, Yellon DM, Evans A, Luc G, Cambou JP, Arveiler D, Cambien F, Latchman DS, Humphries SE, Day IN: Analysis of the association of a heat shock protein70-1 gene promoter polymorphism with myocardial infarction and coronary risk traits. Dis Markers 1998, 13:227-235.