TRANSCRIPTIONAL ACTIVATION OF THE IMMEDIATE-EARLY GENE PIP92 BY SERUMGROWTH-FACTORS REQUIRES BOTH ETS AND CARG-LIKE ELEMENTS

pip92 is an immediate early gene that is transcriptionally activated i n mouse 3T3 fibroblasts upon treatment with serum growth factors or th e tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Here we show th at a 73-base pair pip92 promoter fragment located between base pairs 1 231 and 1158 upstream of the transcription start site is sufficient to mediate transcriptional activation. This promoter fragment contains t wo binding sites for transcription factors of the Ets family and a low affinity binding site for the serum response factor. The minimal sequ ence that mediates serum induction includes at least one copy of the E ts-binding site and a low affinity binding site for the serum response factor. This sequence can interact with at least two proteins in a fi broblast nuclear extract that have binding characteristics of an Ets f amily protein and a serum response factor-like protein. These proteins can bind the pip92-inducible element simultaneously, thus forming a t ernary complex. Furthermore, the same element interacts with recombina nt serum response factor and Elk1 proteins individually as well as sim ultaneously to form a ternary complex. This mode of ternary complex fo rmation is in contrast to the one seen in the promoter of the c-fos pr otooncogene, where formation of the ternary complex is dependent on th e prior assembly of the serum response factor-DNA binary complex. The activation of a number of immediate early genes appears to be mediated through a ternary complex involving members of the Ets family of tran scription factors and the serum response factor. We propose that diffe rent mechanisms can lead to the formation of such ternary complexes.