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Nucleic Acids Research, 1995, Vol. 23, No. 18 3664-3672
© 1995


MOLECULAR BIOLOGY

Tissue-specific regulation of the rabbit 15-lipoxygenase gene in erythroid cells by a transcriptional silencer

Jim O'Prey and Paul R. Harrison*

Beatson Institute for Cancer Research, Cancer Research Campaign Laboratories Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK

*To whom correspondence should be addressed

Received July 3, 1995. Revised August 18, 1995. Accepted August 18, 1995.

The 15-lipoxygenase (lox) gene is expressed in a tissue-specific manner, predominantly in erythroid cells but also in airway epithelial cells and eoslnophils. We demonstrate in this report that the 5' flanking DNA of the 15-lox gene contains sequences which down-regulate its activity in a variety of non-erythrold cell lines but not in two erythroid cell lines. The element has characteristics of a transcriptional ‘silencer’ since it functions in both orientations. The main activity of the silencer has been mapped to the first 900 bp of 5' flanking DNA, which contains nine binding sites for a nuclear factor present in non-erythroid cells but not in erythroid cells. These binding sites have similar sequences and multiple copies of the binding sites confer tissue-specific down-regulation when attached to a minimal lox promoter fragment. The 5' flanking DNA also contains a cluster of three binding sites for the GATA family of transcription factors.


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