Unique organization and involvement of GAGA factors in transcriptional regulation of the Xenopus stromelysin-3 gene

Expression of the matrix metalloproteinase (MMP) gene stromelysin-3 ( ST3 ) has been shown to be tightly associated with cell migration and apoptosis inmammals and amphibians. This contrasts with most other MMP genes. We demonstrate here that the Xenopus ST3 gene also has a structure distinct from other MMP genes, with its C-terminal half (the hemopexin domain) encoded by 4 instead of 6 exons, as in other MMP genes. Our primer extension analysis reveals the existence of two transcription start sites and at least one is needed for transcription of the promoter in transient transfection assays. Furthermore, our deletion analysis has demonstrated a requirement for at least one GAGA factor binding site for promoter function. In vitro DNA binding and mutational studies have provided strong evidence for the participation of GAGA or GAGA-like factors in transcriptional regulation of the frog ST3 gene. This contrasts with regulation of the human ST3 promoter. These results suggest that the ST3 gene evolved prior to most other metalloproteinase genes and uses distinct regulation pathways to achieve similar expression profiles and serve similar functions in mammals and amphibians.