Affiliation:
1. Department of Molecular Genetics, University of Toronto, 1 Kings College Circle, Toronto, Canada M5S 1A8
Abstract
ABSTRACT
The EBNA1 protein of Epstein-Barr virus (EBV) plays several important roles in EBV latent infection, including activating DNA replication from the latent origin of replication (
oriP
) and activating the transcription of other latency genes within the EBV chromatin. These functions require EBNA1 binding to the DS and FR elements within
oriP
, respectively, although how these interactions activate these processes is not clear. We previously identified interactions of EBNA1 with the related nucleosome assembly proteins NAP1 and TAF-I, known to affect the replication and transcription of other chromatinized templates. We have further investigated these interactions, showing that EBNA1 binds directly to NAP1 and to the β isoform of TAF-I (also called SET) and that these interactions greatly increase the solubility of EBNA1 in vitro. These interactions were confirmed in EBV-infected cells, and chromatin immunoprecipitation with these cells showed that NAP1 and TAF-I both localized with EBNA1 to the FR element, while only TAF-I was detected with EBNA1 at the DS element. In keeping with these observations, alteration of the NAP1 or TAF-Iβ level by RNA interference and overexpression inhibited transcriptional activation by EBNA1 in FR reporter assays. In addition, EBNA1-mediated DNA replication was stimulated when TAF-I (but not NAP1) was downregulated and was inhibited by TAF-Iβ overexpression. The results indicate that the interaction of EBNA1 with NAP1 and TAF-I is important for transcriptional activation and that EBNA1 recruits TAF-I to the DS element, where it negatively regulates DNA replication.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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