We have identified a factor in nuclear extracts that binds to the c-fos enhancer. Treatment of A431 cells with epidermal growth factor results in a rapid increase in the level of transcription and a concomitant increase in binding of the factor to the enhancer. Surprisingly, as transcription decreases rapidly, the enhancer-binding activity remains elevated. In addition, although HeLa cells exhibit no detectable transcription of the c-fos gene, they contain significant amounts of binding activity, comparable to those in induced A431 cells. These results suggest that regulation of c-fos transcription involves more than simply an increased level of a factor capable of binding the enhancer. Finally, transcription of c-fos in A431 cells is markedly induced by the tumor promoter TPA and the calcium ionophore A23187, yet neither induced an increased level of the enhancer-binding activity. These agents thus appear to activate c-fos transcription via a mechanism distinct from that used by epidermal growth factors.
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