Multiple regulatory elements control transcription of the peripheral myelin protein zero gene

Abstract

The gene encoding protein zero (P0), the most abundant protein of peripheral nervous system myelin, is expressed uniquely in Schwann cells. Previous studies have demonstrated that much of the cell type specificity of this expression is due to transcriptional control elements in the 1.1- kilobase pair 5'-regulatory region of the gene. We have now analyzed this region and have identified a set of functional elements in the 500 base pairs proximal to the transcription start site. DNA sequence conservation within the 5' regions of the human, mouse, and rat P0 genes correlates closely with the results of promoter deletion analysis 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 promoter were identified by footprinting assays. Functional transcriptional elements were identified within the protected regions in the proximal promoter by mutation and transient transfection analysis in P0-expressing cell lines. The core (or basal) P0 promoter is identified as two regulatory elements, a G/C-rich element that binds nuclear factor Sp1 and a CAAT box that binds NF-Y. These core elements are essential for the transcription observed from the transfected promoter in cultured Schwann cells.