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Molecular and Cellular Biology, November 1999, p. 7610-7620, Vol. 19, No. 11
Human Genome Sciences, Rockville, Maryland
208501; The Wistar Institute,
Philadelphia, Pennsylvania 191042; and
Department of Molecular and Cell Biology, Institute of Medical
Sciences, University of Aberdeen, Aberdeen AB9 1AS,
Scotland3
Received 17 June 1999/Accepted 28 July 1999
The TATA binding protein (TBP) plays a central role in eukaryotic
and archael transcription initiation. We describe the isolation of a
novel 23-kDa human protein that displays 41% identity to TBP and is
expressed in most human tissue. Recombinant TBP-related protein (TRP)
displayed barely detectable binding to consensus TATA box sequences but
bound with slightly higher affinities to nonconsensus TATA sequences.
TRP did not substitute for TBP in transcription reactions in vitro.
However, addition of TRP potently inhibited basal and activated
transcription from multiple promoters in vitro and in vivo. General
transcription factors TFIIA and TFIIB bound glutathione
S-transferase-TRP in solution but failed to stimulate TRP
binding to DNA. Preincubation of TRP with TFIIA inhibited TBP-TFIIA-DNA
complex formation and addition of TFIIA overcame TRP-mediated
transcription repression. TRP transcriptional repression activity was
specifically reduced by mutations in TRP that disrupt the TFIIA binding
surface but not by mutations that disrupt the TFIIB or DNA binding
surface of TRP. These results suggest that TFIIA is a primary target of
TRP transcription inhibition and that TRP may modulate transcription by
a novel mechanism involving the partial mimicry of TBP functions.
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
A Human TATA Binding Protein-Related Protein with
Altered DNA Binding Specificity Inhibits Transcription from Multiple
Promoters and Activators
*
Corresponding author. Mailing address: The Wistar
Institute, 3601 Spruce St., Philadelphia, PA 19104-4205. Phone: (215)
898-9491. Fax: (215) 898-0663. E-mail:
lieberman{at}wista.wistar.upenn.edu.
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