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 journalArticlepeer-review

54 Citations (Scopus)

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

Keywords

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

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