A CONSERVED DOWNSTREAM ELEMENT DEFINES A NEW CLASS OF RNA-POLYMERASE-II PROMOTERS

Although many TATA-less promoters transcribed by RNA polymerase II ini tiate transcription at multiple sites, the regulation of multiple star t site utilization is not understood. Beginning with the prediction th at multiple start site promoters may share regulatory features and usi ng the P-glycoprotein promoter (which can utilize either a single or m ultiple transcription start site(s)) as a model, several promoters wit h analogous transcription windows were grouped and searched for the pr esence of a common DNA element. A downstream protein-binding sequence, MED-1 (Multiple start site Element Downstream), was found in the majo rity of promoters analyzed, Mutation of this element within the P-glyc oprotein promoter reduced transcription by selectively decreasing util ization of downstream start sites. We propose that a new class of RNA polymerase II promoters, those that can utilize a distinctive window o f multiple start sites, is defined by the presence of a downstream MED -1 element.