AN INR-CONTAINING SEQUENCE FLANKING THE TATA BOX OF THE HUMAN C-SIS (PDGF-B) PROTOONCOGENE PROMOTER FUNCTIONS IN CIS AS A COACTIVATOR FOR ITS INTRONIC ENHANCER

High-level activity of the human PDGF-B promoter in choriocarcinoma ce ll lines depends upon an atypical, intronic enhancer-like element whic h does not function with heterologous promoters tested. An extensive s eries of mutant PDGF-B promoter-driven constructs identified a sequenc e flanking the TATA box which is required specifically for enhancer-me diated transcription in human choriocarcinoma cell lines. This element , which we here term an enhancer-dependent cis co-activator (EDC) cont ains an Inr (initiator) consensus sequence upstream of the TATA box wh ich is required, but not sufficient for its function. Requirement for the EDC is cell type-specific, since it was dispensable for enhancer-m ediated transcription in a human breast cancer cell line. Although it lies within the region defined, the TATA box itself is not required fo r EDC function, or for basal promoter function which may derive from a second Inr-like sequence situated at the transcriptional start site. These observations indicate that interactions between some promoter an d enhancer elements may be more complex than that generally described for 'classical' enhancer systems and may suggest an additional functio n for the initiator motif.