MULTIPLE REGULATORY ELEMENTS CONTROL TRANSCRIPTION OF THE PERIPHERAL MYELIN PROTEIN ZERO GENE

The gene encoding protein zero (P-0), the most abundant protein of per ipheral nervous system myelin, is expressed uniquely in Schwann cells. Previous studies have demonstrated that much of the cell type specifi city of this expression is due to transcriptional control elements in the 1.1-kilobase pair 5'-regulatory region of the gene. We have now an alyzed this region and have identified a set of functional elements in the 500 base pairs proximal to the transcription start site. DNA sequ ence conservation within the 5' regions of the human, mouse, and rat P -0 genes correlates closely with the results of promoter deletion anal ysis of the 1.1-kilobase pair region assayed in Schwann cell cultures and reveals a potent proximal region from position -350 to +45. Sites of protein/DNA interaction within the proximal 500 base pairs of the p romoter were identified by footprinting assays. Functional transcripti onal elements were identified within the protected regions in the prox imal promoter by mutation and transient transfection analysis in P-0-e xpressing cell lines, The core (or basal) P-0 promoter is identified a s two regulatory elements, a G/C-rich element that binds nuclear facto r Sp1 and a CAAT box that binds NF-Y. These core elements are essentia l for the transcription observed from the transfected promoter in cult ured Schwann cells.