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 expresse d at different rates in the basal cells of most, if not all, stratifie d epithelia. We have analyzed the 5'-upstream region of the bovine ker atin 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 t ranscriptional 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 experime nts is a consensus AP-1 site. Mutation of this site abolishes the acti vity of tire enhancer and reduces to 25% the activity of the 5.2-kilob ase upstream promoter region. Surprisingly, although the AP-1 presents indistinguishable footprints in all cell types tested, the enhancer i s active only in some of them. Even an oligonucleotide containing the AP-1 region protected from DNase I is active in epithelial cell lines but not in NIH 3T3 fibroblasts, suggesting that this region could cons titute an epithelium-specific AP-1 element. We also show that BK5 does not respond to phorbol ester induction, which suggests that the regul ation of this gene by AP-1 must be complex and probably different from several other suprabasal, AP-1-regulated cellular and viral genes.