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Simple epithelial cells synthesize a different set of keratins than epidermal cells. In experiments reported in this manuscript, we show that the base level of keratin expression in simple epithelial cells is variable for different cell types, and that, in some simple epithelia, this level can be upregulated by increasing the exposure of cells to retinoids, but not glucocorticoids or estradiol. To elucidate the molecular mechanisms underlying simple epithelial keratin gene regulation, we have isolated and characterized a human gene encoding the simple epithelial keratin K7. By examining the possible regulatory elements of this gene and by investigating the behavior of this gene introduced transiently into simple epithelial cells, we have uncovered a possible basis for the differential expression of epidermal and simple epithelial keratin genes.