Cross-Binding of Factors to Functionally Different Promoter Elements in c-fos and Skeletal Actin Genes

Abstract

A conserved 28-base-pair element in the skeletal actin promoter was sufficient to activate muscle-specific expression when placed upstream of a TATA element. This muscle regulatory element (MRE) is similar in structure to the serum response element (SRE), which is present in the promoters of the c-fos proto-oncogene and the nonmuscle actin genes. The SRE can function as a constitutive promoter element. Though the MRE and SRE differed in their tissue-specific expression properties, both elements bound to the same protein factors in vitro. These proteins are the serum response factor (SRF) and the muscle actin promoter factors 1 and 2 (MAPF1 and MAPF2). The SRF and MAPF proteins were resolved by chromatographic procedures, and they differed in their relative affinities for each element. The factors were further distinguished by their distinct, but overlapping, methylation interference footprint patterns on each element. These data indicate that the differences in tissue-specific expression may be due to a complex interaction of protein factors with these sequences.