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Journal of Virology, September 2001, p. 8400-8406, Vol. 75, No. 18
Department of Molecular Microbiology and
Immunology, Keck School of Medicine, University of Southern
California, Los Angeles, California 90033
Received 2 March 2001/Accepted 1 June 2001
The expression of hepatitis B virus (HBV) genes is regulated by a
number of transcription factors. One such factor, Sp1, has two binding
sites in the core promoter and one in its upstream regulatory element,
which is also known as the ENII enhancer. In this study, we have
analyzed the effects of these three Sp1 binding sites on the expression
of HBV genes. Our results indicate that both Sp1 binding sites in the
core promoter are important for the transcription of the core RNA and
the precore RNA. Moreover, while the downstream Sp1 site (the Sp1-1
site) in the core promoter did not affect the transcription of the S
gene and the X gene, the upstream Sp1 site (the Sp1-2 site) in the core
promoter was found to negatively regulate the transcription of the S
gene and the X gene, as removal of the latter led to enhancement of
transcription of these two genes. The Sp1 binding site in the ENII
enhancer (the Sp1-3 site) positively regulates the expression of all of the HBV genes, as its removal by mutation suppressed the expression of
all of the HBV genes. However, the suppressive effect of the Sp1-3 site
mutation on the expression of the S gene and the X gene was abolished
if the two Sp1 sites in the core promoter were also mutated. These
results indicate that Sp1 can serve both as a positive regulator and as
a negative regulator for the expression of HBV genes. This dual
activity may be important for the differential regulation of HBV gene expression.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.18.8400-8406.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Differential Regulation of Hepatitis B Virus Gene
Expression by the Sp1 Transcription Factor
*
Corresponding author. Mailing address: Department of
Molecular Microbiology and Immunology, University of Southern
California Keck School of Medicine, 2011 Zonal Ave., HMR-401, Los
Angeles, CA 90033. Phone: (323) 442-1720. Fax: (323) 442-1721. E-mail: jamesou{at}hsc.usc.edu.
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