title: Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes.
abstract: Death domain-associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein-protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling.
authors: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, 20251 Hamburg, Germany.
authors: Sabrina
authors: S
authors: Schreiner
authors: Carolin
authors: C
authors: Bürck
authors: Mandy
authors: M
authors: Glass
authors: Peter
authors: P
authors: Groitl
authors: Peter
authors: P
authors: Wimmer
authors: Sarah
authors: S
authors: Kinkley
authors: Andreas
authors: A
authors: Mund
authors: Roger D
authors: RD
authors: Everett
authors: Thomas
authors: T
authors: Dobner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017504:Adenovirus E4 Proteins / Q000378:metabolism; D000260:Adenoviruses, Human / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D056970:Co-Repressor Proteins; D004265:DNA Helicases / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006657:Histones / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication; D000075924:X-linked Nuclear Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017504:Adenovirus E4 Proteins; D002843:Chromatin; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; C553319:E1B55K protein, adenovirus; C553318:E4orf6 protein, adenovirus; D006657:Histones; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein
references: Cell. 1981 Oct;26(2 Pt 2):213-20
references: 7332929
references: J Biol Chem. 2003 Nov 21;278(47):47245-52
references: 12968034
references: Oncogene. 2005 Nov 21;24(52):7673-85
references: 16299528
references: J Virol. 2001 Apr;75(7):3089-94
references: 11238835
references: Nat Rev Cancer. 2011 Jun 09;11(7):481-92
references: 21654818
references: Virus Res. 2011 Apr;157(1):47-53
references: 21310198
references: Genome Res. 2010 Mar;20(3):351-60
references: 20110566
references: J Cell Biol. 1999 Oct 18;147(2):221-34
references: 10525530
references: Methods Mol Med. 2007;130:29-39
references: 17401162
references: Cell. 2010 Mar 5;140(5):678-91
references: 20211137
references: J Virol. 2008 Dec;82(24):12543-54
references: 18922870
references: PLoS Pathog. 2010 Jun 03;6(6):e1000935
references: 20532208
references: Genes Dev. 2010 Jun 15;24(12):1253-65
references: 20504901
references: Bioessays. 2004 Sep;26(9):963-77
references: 15351967
references: J Virol. 2008 Aug;82(15):7325-35
references: 18480450
references: Virology. 1982 Jul 30;120(2):510-7
references: 7048730
references: J Virol. 1990 May;64(5):2345-59
references: 2139141
references: J Cell Sci. 2003 Jan 15;116(Pt 2):345-52
references: 12482920
references: Nat Genet. 2009 Aug;41(8):941-5
references: 19633671
references: J Virol. 2010 Apr;84(8):4026-40
references: 20147399
references: J Virol. 2011 Apr;85(8):3950-8
references: 21307207
references: J Cell Sci. 2004 Aug 1;117(Pt 17):3807-20
references: 15252119
references: Eur J Hum Genet. 2008 Feb;16(2):192-201
references: 17957225
references: Curr Top Microbiol Immunol. 1995;199 ( Pt 3):25-32
references: 7555080
references: J Virol. 2007 Jul;81(13):7034-40
references: 17459921
references: Front Biosci. 2001 Sep 01;6:D1054-64
references: 11532604
references: Nucleic Acids Res. 2011 Feb;39(3):889-901
references: 20926393
references: PLoS Pathog. 2011 Jul;7(7):e1002123
references: 21779164
references: J Virol. 2008 Aug;82(15):7252-63
references: 18385237
references: J Virol. 1997 Feb;71(2):1115-23
references: 8995632
references: J Virol. 2006 Sep;80(18):9017-30
references: 16940514
references: EMBO J. 1986 Jul;5(7):1633-44
references: 3743550
references: J Virol. 1999 Oct;73(10):8027-34
references: 10482551
references: Genome Res. 2009 Mar;19(3):404-14
references: 19196724
references: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10635-40
references: 12953102
references: Mol Cell Biol. 2000 Mar;20(5):1784-96
references: 10669754
references: J Virol. 2010 Jul;84(14):7029-38
references: 20484509
references: Curr Top Microbiol Immunol. 2003;272:287-330
references: 12747554
references: Future Microbiol. 2012 Feb;7(2):211-25
references: 22324991
references: Nat Genet. 1997 Oct;17(2):146-8
references: 9326931
references: J Virol. 2009 Sep;83(18):9045-56
references: 19587039
references: Cancer Genomics Proteomics. 2008 Jan-Feb;5(1):63-78
references: 18359981
references: Trends Cell Biol. 2006 Feb;16(2):97-104
references: 16406523
references: J Virol. 2008 Mar;82(6):2642-51
references: 18184699
references: Virology. 1996 Mar 1;217(1):67-75
references: 8599237
references: J Biol Chem. 1993 May 15;268(14):10582-7
references: 8486711
references: J Virol. 1985 Sep;55(3):533-46
references: 3894685
references: Oncogene. 1992 Jan;7(1):171-80
references: 1311061
references: Virology. 2007 Jul 20;364(1):36-44
references: 17367836
references: J Gen Virol. 1977 Jul;36(1):59-74
references: 886304
references: J Virol. 2009 Feb;83(3):1416-21
references: 19004946
references: Curr Top Microbiol Immunol. 2001;259:25-54
references: 11417126
references: J Virol. 2009 Jun;83(11):5329-38
references: 19297475
references: J Biol Chem. 2004 May 7;279(19):20369-77
references: 14990586
references: Gene. 2001 Oct 31;278(1-2):1-23
references: 11707318
references: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6684-9
references: 17428914
references: J Virol. 2011 Sep;85(17):8752-65
references: 21697482
references: J Biol Chem. 2004 Jan 16;279(3):1838-44
references: 14597622
references: Oncogene. 2001 Nov 26;20(54):7847-54
references: 11753667
references: Virology. 2006 Aug 15;352(1):237-52
references: 16750236
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14075-80
references: 20651253
references: J Biol Chem. 1998 Dec 18;273(51):34511-8
references: 9852120
references: J Virol. 2006 Aug;80(16):7995-8005
references: 16873256
references: Genes Dev. 2001 Dec 1;15(23):3104-17
references: 11731475
references: J Virol. 2011 Feb;85(4):1887-92
references: 21123383
references: Oncogene. 2004 Apr 12;23(16):2819-24
references: 15077145
references: Nature. 2002 Jul 18;418(6895):348-52
references: 12124628
references: Nucleic Acids Res. 2012 Dec;40(22):11363-79
references: 23034801
references: Nat Rev Mol Cell Biol. 2002 Jun;3(6):441-52
references: 12042766
references: J Cell Sci. 2002 Aug 15;115(Pt 16):3319-30
references: 12140263
references: Clin Genet. 2006 Jul;70(1):57-62
references: 16813605
references: Curr Top Microbiol Immunol. 1995;199 ( Pt 3):149-75
references: 7555075
references: J Biol Chem. 2004 Nov 12;279(46):48013-23
references: 15339933
references: EMBO J. 1999 Nov 1;18(21):6037-49
references: 10545115
references: J Virol. 2007 Jul;81(14):7629-35
references: 17494079
references: J Biol Chem. 2001 Oct 19;276(42):39103-6
references: 11495919
references: J Virol. 2013 Feb;87(4):2174-85
references: 23221561
references: Mol Cell. 2001 Sep;8(3):713-8
references: 11583632