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PMID: 14557628 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Chromatin remodeling of the Kaposi's sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency.

Journal of virology ·Vol. 77 ·No. 21 ·2003-11-00 ·Pages 11425-35

Lu F, Zhou J, Wiedmer A, Madden K, Yuan Y, Lieberman PM

Abstract

The switch from latent to lytic infection of Kaposi's sarcoma-associated herpesvirus is initiated by the immediate early transcriptional activator protein Rta/open reading frame 50 (ORF50). We examined the transcriptional regulation of the ORF50 core promoter in response to lytic cycle stimulation. We show that the ORF50 promoter is highly responsive to sodium butyrate (NaB) and trichostatin A (TSA), two chemicals known to inhibit histone deacetylases. The NaB and TSA responsive element was mapped to a 70-bp minimal promoter containing an essential GC box that binds Sp1/Sp3 in vitro and in vivo. Micrococcal nuclease mapping studies revealed that a nucleosome is positioned over the transcriptional initiation and the Sp1/3 binding sites. Stimulation with NaB or TSA increased histone acetylation and restriction enzyme accessibility of the ORF50 promoter transcription initiation site. Chromatin immunoprecipitation assay was used to demonstrate that the ORF50 promoter is associated with several different histone deacetylase proteins (including HDAC1, 5, and 7) in latently infected cells. NaB treatment led to the rapid association of Ini1/Snf5, a component of the Swi/Snf family of chromatin remodeling proteins, with the ORF50 promoter. Ectopic expression of the CREB-binding protein (CBP) histone acetyltransferase (HAT) stimulated plasmid-based ORF50 transcription in a HAT-dependent manner, suggesting that CBP recruitment to the ORF50 promoter can be an initiating event for transcription and viral reactivation. Together, these results suggest that remodeling of a stably positioned nucleosome at the transcriptional initiation site of ORF50 is a regulatory step in the transition from latent to lytic infection.

MeSH Terms
Base Sequence Butyrates/pharmacology Cell Line Chromatin/genetics,physiology Chromosomal Proteins, Non-Histone Gene Expression Regulation, Viral Herpesvirus 8, Human/genetics,metabolism,physiology Humans Hydroxamic Acids/pharmacology Immediate-Early Proteins/chemistry,genetics,metabolism Molecular Sequence Data Nucleosomes Promoter Regions, Genetic Trans-Activators/chemistry,genetics,metabolism Transcription Factors Transcription, Genetic Viral Proteins/chemistry,genetics,metabolism Virus Activation Virus Latency
Chemicals
Butyrates Chromatin Chromosomal Proteins, Non-Histone Hydroxamic Acids Immediate-Early Proteins Nucleosomes Rta protein, Human herpesvirus 8 SWI-SNF-B chromatin-remodeling complex Trans-Activators Transcription Factors Viral Proteins trichostatin A
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Lu Fang
The Wistar Institute. Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Zhou Jing
Wiedmer Andreas
Madden Kevin
Yuan Yan
Lieberman Paul M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.77.21.11425-11435.2003
Published
2003-11-00
Pages
11425-35
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC229253
Subset
IM
Grants
NCI NIH HHS · R01 CA085678 · United States
NCI NIH HHS · R01 CA086839 · United States
NCI NIH HHS · CA85678 · United States
NCI NIH HHS · CA86839 · United States
External Links
PubMed source DOI: 10.1128/jvi.77.21.11425-11435.2003 PMC Full Text View journal details
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