THE GENOMIC STRUCTURE OF THE HUMAN AP-2 TRANSCRIPTION FACTOR

The transcription factor AP-2 is encoded by a gene located on chromoso me 6 near the HLA locus. Here we describe the genomic organization of the AP-2 gene including an initial characterization of the promoter. W e have mapped two mRNA initiation sites, the entire exon - intron stru cture and located two polyadenylation sites. The mature AP-2 mRNA is s pliced from 7 exons distributed over a region of 18 kb genomic DNA. A recently cloned inhibitory AP-2 protein is generated by alternative us age of a C-terminal exon. The proline-rich transactivation motif is en coded by a single exon within the N-terminal region in contrast to the complex DNA binding and dimerization motif which involves amino 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 m ediates cell-type-specific expression of a CAT reporter gene in PA-1 h uman teratocarcinoma cells and is inactive in murine F9 teratocarcinom a 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 b inding site is located at position - 622 with respect to the ATG. This site binds specifically to bacterially expressed AP-2 as well as to m ultiple proteins, including AP-2, present in PA-1 and HeLa cell nuclea r extracts. A partial AP-2 promoter fragment including the AP-2 consen sus binding site is approximately 5-fold transactivated by cotransfect ion of an AP-2 expression plasmid.