THE TRANSCRIPTION FACTORS ELK-1 AND SERUM RESPONSE FACTOR INTERACT BYDIRECT PROTEIN-PROTEIN CONTACTS MEDIATED BY A SHORT REGION OF ELK-1

Transcriptional induction of the c-fos gene in response to epidermal g rowth factor stimulation is mediated in part by a ternary nucleoprotei n complex within the promoter consisting of serum response factor (SRF ), p62(TCF)/Elk-1 and the serum response element (SRE). Both SRF and p 62(TCF)/Elk-1 contact the DNA and bind in a cooperative manner to the SRE. In this study, we demonstrate that SRF and Elk-1 interact directl y in the absence of the SRE. A 30-amino-acid peptide from Elk-1 (B-box ) is both necessary and sufficient to mediate protein-protein contacts with SRF. Moreover, the Elk-1 B-box is necessary to enable SRF-depend ent binding of an alternative ETS domain (from the transcription facto r PU.1) to the c-fos SRE. Mutations in either the Elk-1 B-box or the C -terminal half of the SRF DNA-binding domain (core(SRF)) which show re duced ability to form ternary complexes also show greatly reduced prot ein-protein interactions in the absence of the SRE. Our results clearl y demonstrate that direct protein-protein interactions between the tra nscription factors Elk-1 and SRF, in addition to DNA contacts, contrib ute to the formation of a ternary complex on the c-fos SRE. We discuss the wider applicability of our results in describing specific protein -protein interactions between short well-defined transcription factor domains.