On the role of AP2 in epithelial-specific gene expression

Transcription factor AP2 plays an important role in transcription of keratin genes, and it has been suggested that AP2 confers epithelial specificity. Promoters of keratin genes contain AP2 sites, usually within tight clusters of binding sites for other nuclear transcription factors. The role of AP2 was examined by in vitro gel shift analysis, AP2 binding site mutagenesis, and stable and transient transfection experiments. Nonepithelial cells, such as GM10 fibroblasts and melanocytes, neither express keratin nor become phenotypically epithelial when transfected with an AP2-expressing vector. However, in 3T3 and HeLa cells, co-transfection of an AP2-expressing vector increases the level of transcription from keratin gene promoters. This increase requires an intact AP2 binding site. Thus, the role of AP2 in keratin gene expression is quantitative rather than qualitative. AP2 interacts with other transcription factors and may convey extracellular regulatory signals to the transcription complex in the promoters of keratin genes.