Principal role of TRAP/mediator and SWI/SNF complexes in Kaposi's sarcoma-associated herpesvirus RTA-mediated lytic reactivation.
An important step in the herpesvirus life cycle is the switch from latency to lytic reactivation. The RTA transcription activator of Kaposi's sarcoma-associated herpesvirus (KSHV) acts as a molecular switch for lytic reactivation. Here we demonstrate that KSHV RTA recruits CBP, the SWI/SNF chromatin remodeling complex, and the TRAP/Mediator coactivator into viral promoters through interactions with a short acidic sequence in the carboxyl region and that this recruitment is essential for RTA-dependent viral gene expression. The Brg1 subunit of SWI/SNF and the TRAP230 subunit of TRAP/Mediator were shown to interact directly with RTA. Consequently, genetic ablation of these interactions abolished KSHV lytic replication. These results demonstrate that the recruitment of CBP, SWI/SNF, and TRAP/Mediator complexes by RTA is the principal mechanism to direct well-controlled viral gene expression and thereby viral lytic reactivation.
Gwack
Yousang
Y
Tumor Virology Division, New England Regional Primate Research Center, 1 Pine Hill Drive, Southborough, MA 01772-9102, USA.
Baek
Hwa Jin
HJ
Nakamura
Hiroyuki
H
Lee
Sun Hwa
SH
Meisterernst
Michael
M
Roeder
Robert G
RG
Jung
Jae U
JU
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000821:virology; D050882:CREB-Binding Protein; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D004265:DNA Helicases; D004318:Doxycycline / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D046911:Macromolecular Substances; D056892:Mediator Complex; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D025941:Protein Interaction Mapping; D021122:Protein Subunits; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000821:virology; D014764:Viral Proteins / Q000502:physiology*; D014775:Virus Activation; D014779:Virus Replication
D002843:Chromatin; D017874:Immediate-Early Proteins; C460107:MED12 protein, human; D046911:Macromolecular Substances; D056892:Mediator Complex; D009687:Nuclear Proteins; D021122:Protein Subunits; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; C084108:SMARCA4 protein, human; D004265:DNA Helicases; D004318:Doxycycline