The genomic structure of the human AP-2 transcription factor

Abstract

The transcription factor AP-2 is encoded by a gene located on chromosome 6 near the HLA locus. Here we describe the genomic organization of the AP-2 gene including an initial characterization of the promoter. We have mapped two mRNA Initiation sites, the entire exon - intron structure and located two polyadenylatlon sites. The mature AP-2 mRNA is spliced from 7 exons distributed over a region of 18 kb genomic DNA. A recently cloned inhibitory AP-2 protein is generated by alternative usage of a C-tenmlnal exon. The prollne-rlch transactlvatlon motif is encoded by a single exon within the N-termlnal region in contrast to the complex DNA binding and dlmerlzatlon motif which Involves amlno acid residues located on four different exons. The sites of mRNA initiation are located 220 and 271 bases upstream from the ATG translation start site. Although the promoter contains no canonical sequence motifs for basal transcription factors, such as TATA-, CCAAT-or SP-1 boxes, it mediates cell-type-specific expression of a CAT reporter gene in PA-1 human teratocarclnoma cells and is inactive in murine F9 teratocarclnoma cells. We demonstrate that the promoter of the AP-2 gene is subject to positive autoregulation by its own gene product. A consensus AP-2 binding site is located at position - 622 with respect to the ATG. This site binds specifically to bacterlally expressed AP-2 as well as to multiple proteins, including AP-2, present in PA-1 and HeLa cell nuclear extracts. A partial AP-2 promoter fragment including the AP-2 consensus binding site is approximately 5-fold transactlvated by cotransfectlon of an AP-2 expression plasmid.