Effect of AP1 transcription factors on the regulation of transcription in normal human epidermal keratinocytes

The conversion of basal keratinocytes to spinous and granular cells is accompanied by the synthesis of a series of epidermal proteins in a differentiation-specific pattern. The transcription of several of these epidermal marker genes is regulated by activator protein 1 (AP1) interactions at their promoter regions. In the epidermis the various AP1 transcription factors are not present uniformly but appear to have a differentiation-specific distribution. We have explored whether the AP1 regulated expression of the keratin 5, transglutaminase 1, involucrin, and loricrin genes reflects the distribution of the AP1 factors in the epidermis. We have found that c-jun and junD activate and junB downregulates the transcription of both basal and suprabasal genes. The effect of c-jun is exerted through interactions with c-fos at the AP1 motifs in the target promoters, whereas both junB and junD act independently of the binding at the AP1 sites. Thus c-jun and junD act as general positive regulators whereas junB acts as a general suppressor of epidermal-specific genes. Therefore, the differentiation specificity of the API regulation must be determined not only by the formation of distinct DNA/AP1 complexes but also by interactions involving other transcriptional regulators and/or distal regulatory elements.