Characterization of the 5' promoter region of the aminopeptidase N gene in pulmonary type II alveolar cells

Aminopeptidase N (APN, EC 3.4.11.2) is an ectopeptidase expressed in lung at the apical surface of alveolar type II epithelial cells. Its expression is upregulated during fetal lung development. To begin to understand the regulation of APN expression during lung development, the rapid modification of cDNA ends (RACE) was used to clone the 5{dollar}spprime{dollar} end of the major APN transcript in rat lung and alveolar type II cells. The cloned sequence revealed a unique 135 bp untranslated exon which genomic cloning and restriction mapping indicated was located more than 28 kb upstream of the coding sequence. A 269 bp genomic fragment including 97 bp of the untranslated exon functioned as a promoter in transient transfection assays using the A549 human lung adenocarcinoma cell line. Located in this region are DNA elements known to be important for expression of lung specific proteins, including the surfactant-associated proteins A, B, and C and the Clara cell specific protein. Comparison of the APN genomic sequences and gene structure from human and rat suggests that the exon present in the rat lung transcript may result from the use of a previously uncharacterized APN promoter.