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Tissue-specific expression from a compound TATA-dependent and TATA-independent promoter

Garrity, Paul A. and Wold, Barbara J. (1990) Tissue-specific expression from a compound TATA-dependent and TATA-independent promoter. Molecular and Cellular Biology, 10 (11). pp. 5646-5654. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:GARmcb90

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Abstract

We have found that the mouse metallothionein-I (MT-I) gene promoter functions in an unusual, compound manner. It directs both TATA-dependent and TATA-independent modes of transcription in vivo. The TATA-dependent message is initiated at the previously characterized +1 transcription start site and is the predominant species in most tissues. In many cell types it is metal inducible. The TATA-independent initiation sites are distributed over the 160 bp upstream of the previously characterized +1 start site, and the RNA products are present in all tissues examined. Only in testis, however, do the TATA-independent transcripts predominate, accumulating to highest levels in pachytene-stage meiotic cells and early spermatids. Unlike the TATA-dependent +1 transcript, these RNAs are not induced by metal, even in cultured cells in which the +1 species is induced. Transfection studies of site-directed mutants show that destruction of the TATA element drastically alters the ratio of the two RNA classes in cells in which the +1 transcripts normally dominates. In TATA-minus mutants, the TATA-independent RNAs become the most prevalent, although they remain refractory to metal induction. Thus, the MT-I promoter utilizes two different types of core promoter function within a single cell population. The two different types of core promoter respond very differently to environmental stimuli, and the choice between them appears to be regulated in a tissue-specific fashion.


Item Type:Article
Additional Information:Copyright © 1990 by the American Society for Microbiology. Received 7 June 1990/Accepted 7 August 1990. We thank Kelly Thomas, Mel Simon, and Debra Wolgemuth for generous gifts of purified testis cell-type RNAs and mutant RNAs, Richard Palmiter for pMT-I/i, Jim Maher for assistance with mutagenesis, Sean Tavtigian for his initial observations, Tom Novak for the BB62, Paul Mueller, Jeff Miner, and members of the Wold lab for materials and invaluable discussion, and David Anderson, Richard Axel, and Mel Simon for reading the manuscript. This work was supported by grants from the National Institutes of Health, Rita Allen Foundation, and Lucille P. Markey Charitable Trust to B.W. and a National Research Service Award (5 T32 GM 07616-11) from the National Institute of General Medical Sciences to P.G.
Record Number:CaltechAUTHORS:GARmcb90
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:GARmcb90
Alternative URL:http://mcb.asm.org/cgi/content/abstract/10/11/5646
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ID Code:9788
Collection:CaltechAUTHORS
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Deposited On:17 Mar 2008
Last Modified:26 Dec 2012 09:52

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