Identification of phorbol ester response elements in the promoter of Epstein-Barr virus putative lytic switch gene BZLF1.

Flemington E; Speck SH

Division of Tumor Virology, Dana-Farber Cancer Institute, Boston, Massachusetts.

J Virol 64: 1217-26 (1990)

Abstract
The product of the Epstein-Barr virus BZLF1 gene encodes a protein which is related to c-fos, it has been shown to bind specifically to a consensus AP-1 site, and its expression in latently Epstein-Barr virus-infected lymphocytes is sufficient to trigger the viral lytic cycle. We identified several elements within the BZLF1 promoter (Zp) which are responsive to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an inducer of the viral lytic cycle. These elements fall into two classes based on the factors which bind to these sequences and their resulting functional behavior. Four of the elements are homologous (ZI elements) and share homology to a protein-binding domain in the promoter region of the coordinately expressed BRLF1 gene. When cloned upstream of heterologous promoters, the ZI elements function as silencers which exhibit TPA-inducible enhancer activity. A distinct TPA-responsive element (ZII) is located near the TATA box and shares homology with the AP-1-binding site in the c-jun promoter. A synthetic oligonucleotide with a sequence corresponding to the ZII element effectively competes for binding of nuclear factors to the c-jun AP-1 site. Furthermore, we found that a complex of c-jun and c-fos bound to the ZII domain.

Mesh Headings

Base Sequence
Cell Line
Comparative Study
Epstein-Barr Virus*
Exons
Genes, Viral*
Human
Lysogeny*
Molecular Sequence Data
Oligonucleotide Probes
Plasmids
Promoter Regions (Genetics)*
Repetitive Sequences, Nucleic Acid
Restriction Mapping
Sequence Homology, Nucleic Acid
Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S.
Tetradecanoylphorbol Acetate*
Transcription Factors
Transcription, Genetic
Transfection
Viral Proteins

Unique Identifier: 90156519

Chemical Identifiers (Names)

16561-29-8 (Tetradecanoylphorbol Acetate)