Alternative mRNAs encode multiple isoforms of transcription factor AP-2 during murine embryogenesis.

Transcription factor AP-2 has been implicated as an important regulator of gene expression during vertebrate embryogenesis. We report here the cDNA cloning and analysis of mouse embryonic mRNA splice variants encoding four AP-2 isoforms. Isoform 1 is the homolog of the previously known human (HeLa) AP-2. The three new AP-2 isoforms all share the same DNA binding/dimerization domain as isoform 1 but either lack the proline-rich transcriptional activation domain encoded by exon 2 (isoform 2) or have different amino-termini encoded by two previously unknown alternative first coding exons for AP-2 (isoforms 3 and 4). All four AP-2 mRNA variants are present at significant levels between Days 11.5 and 17.5 of mouse embryogenesis. Variants 1, 3, and 4 show qualitatively but not quantitatively similar restricted expression patterns in 8.5-12.5 dpc embryos examined by in situ hybridization. At mid-embryogenesis, variant 3 is the major AP-2 mRNA species in the nervous system and in total embryo RNA but is less prevalent than variants 1 and 4 in the epidermis. The four mRNAs are all induced, although unequally, during differentiation of P19 cells into neural cell types and by cAMP stimulation of primary astrocytes. Variants 1-3 are coexpressed in different ratios in HeLa cells and in three human glioblastoma cell lines. These findings reveal that transcriptional regulation by AP-2 is likely to be more complex than previously assumed given the potential for multiple AP-2 homo- and heterodimeric DNA binding forms.