Lung Cell-specific Expression of the Murine Surfactant Protein A (SP-A) Gene Is Mediated by Interactions between the SP-A Promoter and Thyroid Transcription Factor-1

摘要: Cis-acting elements determining lung epithelial cell-selective transcription of the murine surfactant protein A (SP-A) gene were identified between nucleotide positions −255 and −57. This region SP-A contained sequences consistent with thyroid factor-1 (TTF-1) binding motifs. An SP-A-CAT plasmid containing TTF-1 sites was transcriptionally active in mouse (MLE-15) cells but not HeLa, 3T3, or H441 cells. However, construct activated after cotransfection HeLa a vector expressing recombinant TTF-1, pCMV-TTF-1. Recombinant homeodomain bound to four distinct located nucleotides −231 −168. Proteins nuclear extracts MLE-15 supershifted by antibody. Mutations three this reduced expression transfected transactivation interacts complex protein/DNA 5′-flanking enhancing cell-specific vitro.