ACTIVATOR PROTEIN-1 ACTIVITY IS INVOLVED IN THE REGULATION OF THE CELL-TYPE-SPECIFIC EXPRESSION FROM THE PROXIMAL PROMOTER OF THE HUMAN PROFILAGGRIN GENE
Si. Jang et al., 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 Journal of biological chemistry, 271(39), 1996, pp. 24105-24114
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.