#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA


Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs.


Vyšlo v časopise: Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA. PLoS Pathog 6(6): e32767. doi:10.1371/journal.ppat.1000965
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000965

Souhrn

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs.


Zdroje

1. MocarskiE

ShenkT

PassRF

2007 Cytomegaloviruses. Fields Virology Lippincott Williams & Wilkins 2702 2772

2. StreblowDN

DumortierJ

MosesAV

OrloffSL

NelsonJA

2008 Mechanisms of cytomegalovirus-accelerated vascular disease: induction of paracrine factors that promote angiogenesis and wound healing. Curr Top Microbiol Immunol 325 397 415

3. WallerEC

DayE

SissonsJG

WillsMR

2008 Dynamics of T cell memory in human cytomegalovirus infection. Med Microbiol Immunol 197 83 96

4. CinatlJJr

NevelsM

PaulusC

MichaelisM

2009 Activation of telomerase in glioma cells by human cytomegalovirus: another piece of the puzzle. J Natl Cancer Inst 101 441 443

5. TerhuneSS

SchroerJ

ShenkT

2004 RNAs are packaged into human cytomegalovirus virions in proportion to their intracellular concentration. J Virol 78 10390 10398

6. BresnahanWA

ShenkT

2000 A subset of viral transcripts packaged within human cytomegalovirus particles. Science 288 2373 2376

7. ReevesMB

DaviesAA

McSharryBP

WilkinsonGW

SinclairJH

2007 Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death. Science 316 1345 1348

8. NitzscheA

PaulusC

NevelsM

2008 Temporal Dynamics of Cytomegalovirus Chromatin Assembly in Productively Infected Human Cells. J Virol

9. Cuevas-BennettC

ShenkT

2008 Dynamic Histone H3 Acetylation and Methylation at Human Cytomegalovirus Promoters during Replication in Fibroblasts. J Virol 82 9525 9536

10. ReevesM

MurphyJ

GreavesR

FairleyJ

BrehmA

2006 Autorepression of the human cytomegalovirus major immediate-early promoter/enhancer at late times of infection is mediated by the recruitment of chromatin remodeling enzymes by IE86. J Virol 80 9998 10009

11. IoudinkovaE

ArcangelettiMC

RynditchA

De ContoF

MottaF

2006 Control of human cytomegalovirus gene expression by differential histone modifications during lytic and latent infection of a monocytic cell line. Gene 384 120 128

12. DenslowSA

WadePA

2007 The human Mi-2/NuRD complex and gene regulation. Oncogene 26 5433 5438

13. LakowskiB

RoelensI

JacobS

2006 CoREST-like complexes regulate chromatin modification and neuronal gene expression. J Mol Neurosci 29 227 239

14. SilversteinRA

EkwallK

2005 Sin3: a flexible regulator of global gene expression and genome stability. Curr Genet 47 1 17

15. WangY

ZhangH

ChenY

SunY

YangF

2009 LSD1 is a subunit of the NuRD complex and targets the metastasis programs in breast cancer. Cell 138 660 672

16. GuschinD

WadePA

KikyoN

WolffeAP

2000 ATP-Dependent histone octamer mobilization and histone deacetylation mediated by the Mi-2 chromatin remodeling complex. Biochemistry 39 5238 5245

17. LuoJ

SuF

ChenD

ShilohA

GuW

2000 Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 408 377 381

18. YooYG

KongG

LeeMO

2006 Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1. EMBO J 25 1231 1241

19. ParkJJ

KimYE

PhamHT

KimET

ChungYH

2007 Functional interaction of the human cytomegalovirus IE2 protein with histone deacetylase 2 in infected human fibroblasts. J Gen Virol 88 3214 3223

20. Kuntz-SimonG

ObertG

1995 Sodium valproate, an anticonvulsant drug, stimulates human cytomegalovirus replication. J Gen Virol 76 (Pt 6) 1409 1415

21. TangQ

MaulGG

2003 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 77 1357 1367

22. SaffertRT

KalejtaRF

2006 Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. J Virol 80 3863 3871

23. MichaelisM

SuhanT

ReinischA

ReisenauerA

FleckensteinC

2005 Increased replication of human cytomegalovirus in retinal pigment epithelial cells by valproic acid depends on histone deacetylase inhibition. Invest Ophthalmol Vis Sci 46 3451 3457

24. HummelM

YanS

LiZ

VargheseTK

AbecassisM

2007 Transcriptional reactivation of murine cytomegalovirus ie gene expression by 5-aza-2'-deoxycytidine and trichostatin A in latently infected cells despite lack of methylation of the major immediate-early promoter. J Gen Virol 88 1097 1102

25. WoodhallDL

GrovesIJ

ReevesMB

WilkinsonG

SinclairJH

2006 Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter. J Biol Chem 281 37652 37660

26. NevelsM

PaulusC

ShenkT

2004 Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation. Proc Natl Acad Sci U S A 101 17234 17239

27. PaulusC

KraussS

NevelsM

2006 A human cytomegalovirus antagonist of type I IFN-dependent signal transducer and activator of transcription signaling. Proc Natl Acad Sci U S A 103 3840 3845

28. TaylorTJ

KnipeDM

2004 Proteomics of herpes simplex virus replication compartments: association of cellular DNA replication, repair, recombination, and chromatin remodeling proteins with ICP8. J Virol 78 5856 5866

29. LomonteP

ThomasJ

TexierP

CaronC

KhochbinS

2004 Functional interaction between class II histone deacetylases and ICP0 of herpes simplex virus type 1. J Virol 78 6744 6757

30. GuH

LiangY

MandelG

RoizmanB

2005 Components of the REST/CoREST/histone deacetylase repressor complex are disrupted, modified, and translocated in HSV-1-infected cells. Proc Natl Acad Sci U S A 102 7571 7576

31. RadkovSA

TouitouR

BrehmA

RoweM

WestM

1999 Epstein-Barr virus nuclear antigen 3C interacts with histone deacetylase to repress transcription. J Virol 73 5688 5697

32. KnightJS

LanK

SubramanianC

RobertsonES

2003 Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. J Virol 77 4261 4272

33. BrehmA

NielsenSJ

MiskaEA

McCanceDJ

ReidJL

1999 The E7 oncoprotein associates with Mi2 and histone deacetylase activity to promote cell growth. EMBO J 18 2449 2458

34. LongworthMS

LaiminsLA

2004 The binding of histone deacetylases and the integrity of zinc finger-like motifs of the E7 protein are essential for the life cycle of human papillomavirus type 31. J Virol 78 3533 3541

35. LongworthMS

WilsonR

LaiminsLA

2005 HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs. EMBO J 24 1821 1830

36. MoormanNJ

CristeaIM

TerhuneSS

RoutMP

ChaitBT

2008 Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Cell Host Microbe 3 253 262

37. TerhuneS

TorigoiE

MoormanN

SilvaM

QianZ

2007 Human cytomegalovirus UL38 protein blocks apoptosis. J Virol 81 3109 3123

38. XuanB

QianZ

TorigoiE

YuD

2009 Human cytomegalovirus protein pUL38 induces ATF4 expression, inhibits persistent JNK phosphorylation, and suppresses endoplasmic reticulum stress-induced cell death. J Virol 83 3463 3474

39. YuD

SilvaMC

ShenkT

2003 Functional map of human cytomegalovirus AD169 defined by global mutational analysis. Proc Natl Acad Sci U S A 100 12396 12401

40. DunnW

ChouC

LiH

HaiR

PattersonD

2003 Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci U S A 100 14223 14228

41. MitchellDP

SavarynJP

MoormanNJ

ShenkT

TerhuneSS

2009 Human cytomegalovirus UL28 and UL29 open reading frames encode a spliced mRNA and stimulate accumulation of immediate-early RNAs. J Virol 83 10187 10197

42. RomanowskiMJ

ShenkT

1997 Characterization of the human cytomegalovirus irs1 and trs1 genes: a second immediate-early transcription unit within irs1 whose product antagonizes transcriptional activation. J Virol 71 1485 1496

43. BresnahanWA

HultmanGE

ShenkT

2000 Replication of wild-type and mutant human cytomegalovirus in life-extended human diploid fibroblasts. J Virol 74 10816 10818

44. KinsellaTM

NolanGP

1996 Episomal vectors rapidly and stably produce high-titer recombinant retrovirus. Hum Gene Ther 7 1405 1413

45. YuD

SmithGA

EnquistLW

ShenkT

2002 Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J Virol 76 2316 2328

46. CristeaIM

CarrollJW

RoutMP

RiceCM

ChaitBT

2006 Tracking and elucidating alphavirus-host protein interactions. J Biol Chem 281 30269 30278

47. CristeaIM

WilliamsR

ChaitBT

RoutMP

2005 Fluorescent proteins as proteomic probes. Mol Cell Proteomics 4 1933 1941

48. KrutchinskyAN

ZhangW

ChaitBT

2000 Rapidly switchable matrix-assisted laser desorption/ionization and electrospray quadrupole-time-of-flight mass spectrometry for protein identification. J Am Soc Mass Spectrom 11 493 504

49. KrutchinskyAN

KalkumM

ChaitBT

2001 Automatic identification of proteins with a MALDI-quadrupole ion trap mass spectrometer. Anal Chem 73 5066 5077

50. LuoY

LiT

YuF

KramerT

CristeaIM

2009 Resolving the Composition of Protein Complexes Using a MALDI LTQ Orbitrap. J Am Soc Mass Spectrom

51. ZhuH

ShenY

ShenkT

1995 Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J Virol 69 7960 7970

52. FengX

SchroerJ

YuD

ShenkT

2006 Human cytomegalovirus pUS24 is a virion protein that functions very early in the replication cycle. J Virol 80 8371 8378

53. NaldiniL

BlomerU

GallayP

OryD

MulliganR

1996 In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272 263 267

54. NaldiniL

BlomerU

GageFH

TronoD

VermaIM

1996 Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci U S A 93 11382 11388

55. LuF

ZhouJ

WiedmerA

MaddenK

YuanY

2003 Chromatin remodeling of the Kaposi's sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency. J Virol 77 11425 11435

56. PoonAP

GuH

RoizmanB

2006 ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression. Proc Natl Acad Sci U S A 103 9993 9998

57. ZhangY

JonesC

2001 The bovine herpesvirus 1 immediate-early protein (bICP0) associates with histone deacetylase 1 to activate transcription. J Virol 75 9571 9578

58. GlozakMA

SetoE

2007 Histone deacetylases and cancer. Oncogene 26 5420 5432

59. WolfDG

CourcelleCT

PrichardMN

MocarskiES

2001 Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc Natl Acad Sci U S A 98 1895 1900

60. KroskyPM

BaekMC

CoenDM

2003 The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J Virol 77 905 914

61. MitchellDP

SavarynJP

MoormanNJ

ShenkT

TerhuneSS

2009 Human cytomegalovirus UL28 and UL29 open reading frames encode a spliced mRNA and stimulate accumulation of immediate-early RNAs. J Virol

62. MoormanNJ

Sharon-FrilingR

ShenkT

CristeaIM

2009 A targeted spatial-temporal proteomic approach implicates multiple cellular trafficking pathways in human cytomegalovirus virion maturation. Mol Cell Proteomics

63. CostesSV

DaelemansD

ChoEH

DobbinZ

PavlakisG

2004 Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys J 86 3993 4003

64. NevelsM

BruneW

ShenkT

2004 SUMOylation of the human cytomegalovirus 72-kilodalton IE1 protein facilitates expression of the 86-kilodalton IE2 protein and promotes viral replication. J Virol 78 7803 7812

65. GrovesI

ReevesM

SinclairJ

2009 Lytic infection of permissive cells with human cytomegalovirus is regulated by an intrinsic “pre-immediate early” repression of viral gene expression mediated by histone post-translational modification. J Gen Virol

66. GuoW

ShanB

KlingsbergRC

QinX

LaskyJA

2009 Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition. Am J Physiol Lung Cell Mol Physiol 297 L864 870

67. PegoraroG

KubbenN

WickertU

GohlerH

HoffmannK

2009 Ageing-related chromatin defects through loss of the NURD complex. Nat Cell Biol 11 1261 1267

68. Ramirez-CarrozziVR

NazarianAA

LiCC

GoreSL

SridharanR

2006 Selective and antagonistic functions of SWI/SNF and Mi-2beta nucleosome remodeling complexes during an inflammatory response. Genes Dev 20 282 296

69. DeMerittIB

MilfordLE

YurochkoAD

2004 Activation of the NF-kappaB pathway in human cytomegalovirus-infected cells is necessary for efficient transactivation of the major immediate-early promoter. J Virol 78 4498 4507

70. NetterwaldJ

YangS

WangW

GhannyS

CodyM

2005 Two gamma interferon-activated site-like elements in the human cytomegalovirus major immediate-early promoter/enhancer are important for viral replication. J Virol 79 5035 5046

71. WaltersMS

ErazoA

KinchingtonPR

SilversteinS

2009 Histone Deacetylase 1 and 2 are Phosphorylated at Novel Sites During Varicella Zoster Virus Infection. J Virol

72. Miccio A, Wang Y, Hong W, Gregory GD, Wang H, et al. NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development. EMBO J 29 442 456

73. LeeSB

OuDS

LeeCF

JuanLJ

2009 Gene-specific transcriptional activation mediated by the p150 subunit of the chromatin assembly factor 1. J Biol Chem 284 14040 14049

74. TakamiY

OnoT

FukagawaT

ShibaharaK

NakayamaT

2007 Essential role of chromatin assembly factor-1-mediated rapid nucleosome assembly for DNA replication and cell division in vertebrate cells. Mol Biol Cell 18 129 141

75. KitagawaH

FujikiR

YoshimuraK

MezakiY

UematsuY

2003 The chromatin-remodeling complex WINAC targets a nuclear receptor to promoters and is impaired in Williams syndrome. Cell 113 905 917

76. FujitaN

JayeDL

KajitaM

GeigermanC

MorenoCS

2003 MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113 207 219

77. ZhangH

SinghRR

TalukderAH

KumarR

2006 Metastatic tumor antigen 3 is a direct corepressor of the Wnt4 pathway. Genes Dev 20 2943 2948

78. MolliPR

SinghRR

LeeSW

KumarR

2008 MTA1-mediated transcriptional repression of BRCA1 tumor suppressor gene. Oncogene 27 1971 1980

79. BrowneEP

WingB

ColemanD

ShenkT

2001 Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J Virol 75 12319 12330

80. CasavantNC

LuoMH

RosenkeK

WinegardnerT

ZurawskaA

2006 Potential role for p53 in the permissive life cycle of human cytomegalovirus. J Virol 80 8390 8401

81. HannemannH

RosenkeK

O'DowdJM

FortunatoEA

2009 The presence of p53 influences the expression of multiple human cytomegalovirus genes at early times postinfection. J Virol 83 4316 4325

82. LuZ

HuX

LiY

ZhengL

ZhouY

2004 Human papillomavirus 16 E6 oncoprotein interferences with insulin signaling pathway by binding to tuberin. J Biol Chem 279 35664 35670

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2010 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#