Cooperative function of two separate enhancers of the human epidermal growth factor receptor proto-oncogene

Two separate enhancers were identified both upstream and downstream of the promoter of the human epidermal growth factor receptor gene. Transcriptional enhancer activity was found to be associated with a region 1172 and 852 base pairs upstream of the most upstream RNA start site, and within a 530-base pair fragment located in the first intron about 2000 base pairs downstream of the most upstream RNA start site. These two separate enhancers stimulated promoter activity cooperatively in HeLa cells synthesizing the epidermal growth factor receptor. The enhancer downstream of the promoter functioned only in the presence of the other upstream enhancer. Several areas of sequences homology with viral and cellular enhancers were noted in both the upstream and downstream enhancers. The region essential for the downstream enhancer activity has 10 nuclear factor-binding sites.