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 vi tro transcription experiments we show that the abundance of the mRNA a nd the specificity of the expression are regulated primarily at the le vel of transcription. We found that the 5'-flanking sequences control the transcription in a keratinocyte-specific mode and that as little a s 116 base pairs preceding the mRNA initiation site is sufficient to r estrict the transcription to epidermal cells in vitro. This specificit y depends critically on the presence of an activator protein 1 (AP1) m otif at position -77. Binding of c-jun/c-fos heterodimers to this sequ ence confers high levels of expression to the reporter constructs in c ultured epidermal keratinocytes, while having little effect in HeLa ce lls. The transactivating properties of c-jun are essential in this pro cess. On the other hand, junB and junD, which are involved in transact ivating the transcription of earlier epidermal differentiation markers , control profilaggrin expression through a pathway which does not dep end 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, multi pathway regulation of the profilaggrin gene expression.