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Nucleic Acids Research, 1988, Vol. 16, No. 15 7527-7544
© 1988

Articles

Multiple nuclear factors interact with promoter sequences of the urokinase-type plasminogen activator gene

Dietmar von der Ahe, David Pearson, Jun-ichi Nakagawa, Bhanu Rajput and Yoshikuni Nagamine

Fredrich Miescher-lnstitut PO Box 2543, CH-4002 Basel, Switzerland

Received March 16, 1988. Revised June 28, 1988. Accepted June 28, 1988.

To characterize proteins that bind to the cyclic AMP inducible promoter of the urokinase-type plasminogen activator gene, we performed a DNAase I footprinting analysis. Within 500 nucleotides upstream of the transcription start site we found eight protected regions due to at least four different binding proteins. Among these is a single binding site for the transcription factor CTF/NF1, which is flanked on each side by two conserved binding sites for the transcription factor Spl. A region at –380, which shares a similarity with sequences observed in the corresponding regions of other cyclic AMP regulated genes, was protected. This binding site contains a sequence of ten nucleotides which is repeated further upstream at –480 and also protected against DMAase I digestion. Comparisons of extracts from four different cell lines revealed that all DMA binding factors are present in nuclei of uPA expressing and nonexpressing cells. Mechanism underlying hormonal regulation of the gene is discussed.


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