Structure of the Mesothelin/MPF gene and characterization of its promoter.

Mesothelin is a cell-surface antigen of unknown function that is expressed in a highly tissue-specific manner. Expression of the protein is limited to mesothelium, the tissue forming the pleural, pericardial, and peritoneal membranes. The purpose of this study was to characterize the gene and identify elements responsible for its transcription. The gene contains an 1884-bp open reading frame encoded by 15 exons occupying 8 kb of human chromosome 16. An 1850-bp region of genomic DNA at the 5' end of the gene encompassing the proposed transcriptional start site was cloned. This region lacks a TATA box and other regulatory elements such as SP1 sites, which are commonly found in promoters. Transient transfection analyses demonstrated that mesothelium-specific control elements are present within the 1.85-kb region. Minimal constitutive promoter elements were localized to a 317-bp region. Tissue-specific enhancer elements upstream of the minimal promoter were found to activate transcription from the homologous and a heterologous promoter in a position- and orientation-independent manner.