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PMID: 1331521 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The Epstein-Barr virus immediate-early promoter BRLF1 can be activated by the cellular Sp1 transcription factor.

Journal of virology ·Vol. 66 ·No. 12 ·1992-12-00 ·Pages 7282-92

Zalani S, Holley-Guthrie EA, Gutsch DE, Kenney SC

Abstract

Disruption of viral latency in Epstein-Barr virus-infected cells is mediated through the activation of the BZLF1 (Z) immediate-early gene product. The Z protein can be derived from either of two promoters: the BZLF1 promoter, which directs transcription of a 1.0-kb mRNA encoding the Z gene product alone, or the upstream BRLF1 promoter, which directs transcription of a 2.8-kb bicistronic mRNA encoding the BRLF1 and BZLF1 immediate-early proteins. In this study we have examined the regulation of the BRLF1 promoter by viral and cellular factors. We found that the BRLF1 promoter is autoregulated by the BRLF1 transactivator through a nonbinding mechanism. We show that the BRLF1 (but not the BZLF1) promoter is highly responsive to the Sp1 transcription factor. Sp1 activation of the BRLF1 promoter is mediated through a consensus Sp1-binding site located from -39 to -44 (relative to the mRNA start site). We demonstrate that the BRLF1 promoter has high constitutive activity in C-33 cells (an epithelial cell line) and that the proximal Sp1-binding site is required for this activity. Despite the ubiquitous presence of Sp1 in many cell types, we found that the BRLF1 promoter has essentially no activity in lymphoid cell lines, suggesting that factors other than Sp1 may negatively regulate the BRLF1 promoter in these cells. Our findings demonstrate that the two potential promoters directing BZLF1 transcription are differentially regulated and that Sp1 can activate the BRLF1 promoter but not the BZLF1 promoter.

Related Genes
BRLF1 BZLF1
MeSH Terms
Animals Base Sequence Binding Sites Cell Line Chloramphenicol O-Acetyltransferase/genetics,metabolism Gene Expression Regulation, Viral HeLa Cells Herpesvirus 4, Human/genetics Humans Methylation Molecular Sequence Data Mutagenesis, Site-Directed Plasmids Promoter Regions, Genetic Recombinant Proteins/metabolism Sp1 Transcription Factor/metabolism TATA Box Trans-Activators/metabolism Transcription Factors/metabolism Transfection Tumor Cells, Cultured
Chemicals
Recombinant Proteins Sp1 Transcription Factor Trans-Activators Transcription Factors Chloramphenicol O-Acetyltransferase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zalani S
Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295.
Holley-Guthrie E A
Gutsch D E
Kenney S C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.66.12.7282-7292.1992
Published
1992-12-00
Pages
7282-92
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC240432
Subset
IM
Grants
NCI NIH HHS · K08-CA01229 · United States
NCI NIH HHS · P01-CA19014 · United States
External Links
PubMed source DOI: 10.1128/JVI.66.12.7282-7292.1992 PMC Full Text View journal details
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