INTERACTION BETWEEN A NOVEL F9-SPECIFIC FACTOR AND OCTAMER-BINDING PROTEINS IS REQUIRED FOR CELL-TYPE-RESTRICTED ACTIVITY OF THE FIBROBLASTGROWTH-FACTOR-4 ENHANCER

Understanding how diverse transcription patterns are achieved through common factor binding elements is a fundamental question that underlie s much of developmental and cellular biology. One example is provided by the fibroblast growth factor 4 (FGF-4) gene, whose expression is re stricted to specific embryonic tissues during development and to undif ferentiated embryonal carcinoma cells in tissue culture. Analysis of t he cis-and trans-acting elements required for the activity of the prev iously identified FGF-4 enhancer in F9 embryonal carcinoma cells showe d that enhancer function depends on sequences that bind Spl and ubiqui tous as well as F9-specific octamer-binding proteins. However, sequenc es immediately upstream of the octamer motif, which conform to a bindi ng site for the high-mobility group (HMG) domain factor family, were a lso critical to enhancer function. We have identified a novel F9-speci fic factor, Fx, which specifically recognizes this motif. Fx formed co mplexes with either Oct-1 or Oct-3 in a template-dependent manner. The ability of different enhancer variants to form the Oct-Fx complexes c orrelated with enhancer activity, indicating that these complexes play an essential role in transcriptional activation of the FGF-4 gene. Th us, while FGF-4 enhancer function is octamer site dependent, its devel opmentally restricted activity is determined by the interaction of oct amer-binding proteins with the tissue-specific factor Fx.