Analysis of the control of expression and tissue specificity of the keratin 5 gene, characteristic of basal keratinocytes. Fundamental role of an AP-1 element.

The keratin 5 gene presents a complex regulation, since it is expressed at different rates in the basal cells of most, if not all, stratified epithelia. We have analyzed the 5'-upstream region of the bovine keratin 5 (BK5) gene and found that the 5.2 kilobases preceding the gene mimic in vitro the cell type-specific expression of BK5. Most of the transcriptional activity maps to an enhancer located between positions -762 and -1009. The only regulatory element found in this enhancer by electrophoretic mobility shift, competition, and footprinting experiments is a consensus AP-1 site. Mutation of this site abolishes the activity of the enhancer and reduces to 25% the activity of the 5.2-kilobase upstream promoter region. Surprisingly, although the AP-1 presents indistinguishable footprints in all cell types tested, the enhancer is active only in some of them. Even an oligonucleotide containing the AP-1 region protected from DNase I is active in epithelial cells lines but not in NIH 3T3 fibroblasts, suggesting that this region could constitute an epithelium-specific AP-1 element. We also show that BK5 does not respond to phorbol ester induction, which suggests that the regulation of this gene by AP-1 must be complex and probably different from several other suprabasal, AP-1-regulated cellular and viral genes.