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

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 -