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Journal of Virology, March 2001, p. 2301-2313, Vol. 75, No. 5
Departments of Internal
Medicine1 and Microbiology and
Immunology2 and Program in Cellular and
Molecular Biology,3 University of Michigan
Medical Center, Ann Arbor, Michigan 48109-0640
Received 1 March 2000/Accepted 7 December 2000
GLI proteins are involved in the development of mice, humans,
zebrafish, Caenorhabditis elegans, Xenopus, and
Drosophila. While these zinc finger-containing proteins
bind to TG-rich promoter elements and are known to regulate gene
expression in C. elegans and Drosophila,
mechanistic understanding of how regulation is mediated through
naturally occurring transcriptional promoters is lacking. One isoform
of human GLI-2 appears to be identical to a factor previously called
Tax helper protein (THP), thus named due to its ability to interact
with a TG-rich element in the human T-lymphotropic virus type 1 (HTLV-1) enhancer thought to mediate transcriptional stimulation by the
Tax protein of HTLV-1. We now demonstrate that, working through its
TG-rich binding site and adjacent elements, GLI-2/THP actually
suppresses gene expression driven by the HTLV-1 promoter. GLI-2/THP has
no effect on the HTLV-2 promoter, activates expression from the
promoters of human immunodeficiency virus types 1 and (HIV-1 and -2),
and stimulates HIV-1 replication. Both effective suppression and
activation of gene expression and viral replication require the first
of the five zinc fingers, which is not necessary for DNA binding, to be
intact. Thus, not only can GLI-2/THP either activate or suppress gene
expression, depending on the promoter, but the same domain (first zinc
finger) mediates both effects. These findings suggest a role for GLI-2
in retroviral gene regulation and shed further light on the mechanisms
by which GLI proteins regulate naturally occurring promoters.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.5.2301-2313.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
GLI-2 Modulates Retroviral Gene
Expression
*
Corresponding author. Mailing address: 5220 MSRB III,
1150 W. Medical Center Dr., Ann Arbor, MI 48109-0640. Phone: (734)
647-1786. Fax: (734) 764-0101. E-mail: Dmarkov{at}umich.edu.
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