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 (S T3) has been shown to be tightly associated with cell migration and ap optosis in mammals and amphibians. This contrasts with most other MMP genes. We demonstrate here that the Xenopus ST3 gene also has a struct ure distinct from other MMP genes, with its C-terminal half (the hemop exin domain) encoded by 4 instead of 6 exons, as in other MMP genes. G ear primer extension analysis reveals the existence of two transcripti on start sites and at least one is needed for transcription of the pro moter in transient transfection assays. Furthermore, our deletion anal ysis has demonstrated a requirement for at least one GAGA factor bindi ng site for promoter function. In vitro DNA binding and mutational stu dies have provided strong evidence for the participation of GAGA ok GA GA-like factors in transcriptional regulation of the frog ST3 gene. Th is contrasts with regulation of the human ST3 promoter. These results suggest that the ST3 gene evolved prior to most other metalloproteinas e genes and uses distinct regulation pathways to achieve similar expre ssion profiles and serve similar functions in mammals and amphibians.