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Mol Cell Biol, May 1998, p. 2535-2544, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Transcriptional Activation of the Integrated Chromatin-Associated
Human Immunodeficiency Virus Type 1 Promoter
Aboubaker
El Kharroubi,
Graziella
Piras,
Ralf
Zensen, and
Malcolm A.
Martin*
Laboratory of Molecular Microbiology,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, Maryland 20892
Received 2 October 1997/Returned for modification 7 November
1997/Accepted 4 February 1998
The regulation of human immunodeficiency virus type 1 (HIV-1) gene
expression involves a complex interplay between cellular transcription
factors, chromatin-associated proviral DNA, and the virus-encoded
transactivator protein, Tat. Here we show that Tat transactivates the
integrated HIV-1 long terminal repeat (LTR), even in the absence of
detectable basal promoter activity, and this transcriptional activation
is accompanied by chromatin remodeling downstream of the transcription
initiation site, as monitored by increased accessibility to restriction
endonucleases. However, with an integrated promoter lacking both Sp1
and NF-
B sites, Tat was unable to either activate transcription or
induce changes in chromatin structure even when it was tethered to the
HIV-1 core promoter upstream of the TATA box. Tat responsiveness was observed only when Sp1 or NF-
B was bound to the promoter, implying that Tat functions subsequent to the formation of a specific
transcription initiation complex. Unlike Tat, NF-
B failed to
stimulate the integrated transcriptionally silent HIV-1 promoter.
Histone acetylation renders the inactive HIV-1 LTR responsive to
NF-
B, indicating that a suppressive chromatin structure must be
remodeled prior to transcriptional activation by NF-
B. Taken
together, these results suggest that Sp1 and NF-
B are required for
the assembly of transcriptional complexes on the integrated viral
promoter exhibiting a continuum of basal activities, all of which are
fully responsive to Tat.
*
Corresponding author. Mailing address: Laboratory of
Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 4, Room 315, 4 Center
Dr., Bethesda, MD 20892. Phone: (301) 496-4012. Fax: (301) 402-0226. E-mail: maln{at}nih.gov.

Present address: Mammalian Developmental Biology Laboratory, ABL
Basic Research Program, Frederick, MD 21702.
Mol Cell Biol, May 1998, p. 2535-2544, Vol. 18, No. 5
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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