Elk-1 Can Recruit SRF to Form a Ternary Complex Upon the Serum Response Element

The initial genomic response to serum growth factors is the transcriptional activation of a set of immediate-early genes. Serum-induced transcriptional activation of several of these genes involves the formation of a ternary complex that includes the serum response factor (SRF), a 62 kDa ternary complex factor (TCF) and a serum response element (SRE). TCF alone does not bind the SRE of the protooncogene c-fos, but requires the prior assembly of the SRF-SRE binary complex for it to be recruited into a ternary complex. Here we show that this SRF-SRE binary complex is not an obligatory prerequisite for the formation of a serum responsive ternary complex. We demonstrate that Elk-1, which has properties of TCF can recruit SRF into a ternary complex on elements that do not support formation of the SRF-DNA binary complex. We also show that for two immediate-early genes, pip92 and nur77, formation of the ternary complex may occur without the prior assembly of SRF-DNA binary complex. Finally, we show that the ability of different sequences to support formation of Elk-l-SRF-DNA ternary complex in vitro correlates with their ability to respond to serum growth factors in vivo. Our results suggest that a much broader range of DNA sequences than the consensus SRF and TCF binding sites can support ternary complex formation, and by inference, serum induction. Possible implications of these results are discussed.