Identification of a third protein factor which binds to the Rous sarcoma virus LTR enhancer: possible homology with the serum response factor.

We have identified a new protein factor (EFIII) in nuclear extracts of quail fibroblasts and chick embryos which binds specifically in vitro to a 26-bp region of the Rous sarcoma virus (RSV) long terminal repeat (LTR) enhancer. The EFIII binding site in the RSV LTR exhibits a strong sequence homology to the serum response element (SRE). The SRE is a 22-bp cis-acting DNA sequence element, first identified upstream of the human c-fos gene, which can confer serum inducibility to heterologous promotors. The binding site for EFIII in the RSV LTR enhancer is also of interest because this region has been implicated in mediating trans-activation of the RSV LTR enhancer by the protein product of the v-fos gene. We show that avian EFIII binds with equal efficiency to both its binding sites in the RSV LTR and the human c-fos SRE. A dyad symmetry element in the c-fos SRE, previously shown to be critical for binding of the cognate human serum response factor (SRF), is also critical for EFIII binding to the LTR SRE-homologous sequences; similarly, EFIII and the human SRF exhibit identical protein-DNA contacts with their corresponding recognition sequences. We suggest that EFIII may be the avian homolog of the mammalian SRF and, in fact, have evidence to indicate that the RSV LTR is serum responsive.