TY - JOUR
T1 - Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes
AU - Schreiner, Sabrina
AU - Bürck, Carolin
AU - Glass, Mandy
AU - Groitl, Peter
AU - Wimmer, Peter
AU - Kinkley, Sarah
AU - Mund, Andreas
AU - Everett, Roger D
AU - Dobner, Thomas
PY - 2013/4/1
Y1 - 2013/4/1
N2 - 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.
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 - Adaptor Proteins, Signal Transducing/metabolism
KW - Adenovirus E4 Proteins/metabolism
KW - Adenoviruses, Human/genetics
KW - Cell Line
KW - Chromatin/chemistry
KW - DNA Helicases/metabolism
KW - Gene Expression Regulation, Viral
KW - Histones/metabolism
KW - Humans
KW - Nuclear Proteins/metabolism
KW - Promoter Regions, Genetic
KW - RNA, Messenger/biosynthesis
KW - Ubiquitin-Protein Ligases/metabolism
KW - Viral Proteins/metabolism
KW - Virus Replication
KW - X-linked Nuclear Protein
U2 - 10.1093/nar/gkt064
DO - 10.1093/nar/gkt064
M3 - Journal article
C2 - 23396441
SN - 0305-1048
VL - 41
SP - 3532
EP - 3550
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 6
ER -