Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene

The human profilaggrin gene is expressed in the granular layer during the late stages of terminal differentiation of the epidermis. In in vitro transcription experiments we show that the abundance of the mRNA and the specificity of the expression are regulated primarily at the level of transcription. We found that the 5'-flanking sequences control the transcription in a keratinocyte-specific mode and that as little as 116 base pairs preceding the mRNA initiation site is sufficient to restrict the transcription to epidermal cells in vitro. This specificity depends critically on the presence of an activator protein 1 (AP1) motif at position -77. Binding of c-jun/c-fos heterodimers to this sequence confers high levels of expression to the reporter constructs in cultured epidermal keratinocytes, while having little effect in HeLa cells. The transactivating properties of c-jun are essential in this process. On the other hand, junB and junD, which are involved in transactivating the transcription of earlier epidermal differentiation markers, control profilaggrin expression through a pathway which does not depend on a direct binding at the AP1 site and is not cell-type specific. These data indicate that AP1 factors are involved in a complex, multipathway regulation of the profilaggrin gene expression.