Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

Sabrina Schreiner, Carolin Buerck, Mandy Glass, Peter Groitl, Peter Wimmer, Sarah Kinkley, Andreas Mund, Roger Everett, Thomas Dobner

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)3532-3550
Number of pages19
JournalNucleic Acids Research
Volume41
Issue number6
DOIs
Publication statusPublished - 8 Feb 2013
Externally publishedYes

Fingerprint

Human Adenoviruses
Chromatin
Chromatin Assembly and Disassembly
Gene Expression
Adenoviridae
Proteins
Cullin Proteins
Histone Deacetylases
Ubiquitin-Protein Ligases
Thalassemia
Viral Genes
Viral Proteins
Open Reading Frames
Adenosine Triphosphatases
Sucrose
Adenosine Triphosphate
Viruses
Genes

Keywords

  • gene expression
  • chromatin
  • viruses
  • alpha-thalassemia/mental retardation syndrome
  • nondeletion type
  • x-linked
  • complex
  • gene regulation
  • epigenetics

Cite this

Schreiner, S., Buerck, C., Glass, M., Groitl, P., Wimmer, P., Kinkley, S., ... Dobner, T. (2013). Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes. Nucleic Acids Research, 41(6), 3532-3550. https://doi.org/10.1093/nar/gkt064
Schreiner, Sabrina ; Buerck, Carolin ; Glass, Mandy ; Groitl, Peter ; Wimmer, Peter ; Kinkley, Sarah ; Mund, Andreas ; Everett, Roger ; Dobner, Thomas. / Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes. In: Nucleic Acids Research. 2013 ; Vol. 41, No. 6. pp. 3532-3550.
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Schreiner, S, Buerck, C, Glass, M, Groitl, P, Wimmer, P, Kinkley, S, Mund, A, Everett, R & Dobner, T 2013, 'Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes', Nucleic Acids Research, vol. 41, no. 6, pp. 3532-3550. https://doi.org/10.1093/nar/gkt064

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes. / Schreiner, Sabrina; Buerck, Carolin; Glass, Mandy; Groitl, Peter; Wimmer, Peter; Kinkley, Sarah; Mund, Andreas; Everett, Roger; Dobner, Thomas.

In: Nucleic Acids Research, Vol. 41, No. 6, 08.02.2013, p. 3532-3550.

Research output: Contribution to journalArticle

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T1 - Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

AU - Schreiner, Sabrina

AU - Buerck, Carolin

AU - Glass, Mandy

AU - Groitl, Peter

AU - Wimmer, Peter

AU - Kinkley, Sarah

AU - Mund, Andreas

AU - Everett, Roger

AU - Dobner, Thomas

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AB - 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.

KW - gene expression

KW - chromatin

KW - viruses

KW - alpha-thalassemia/mental retardation syndrome

KW - nondeletion type

KW - x-linked

KW - complex

KW - gene regulation

KW - epigenetics

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M3 - Article

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