Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene

Ramgopal Margana, Kiflu Berhane, M. Nurul Alam, Vijayakumar Boggaram
2000 American Journal of Physiology - Lung cellular and Molecular Physiology  
Margana, Ramgopal, Kiflu Berhane, M. Nurul Alam, and Vijayakumar Boggaram. Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L477-L484, 2000.-Surfactant protein B (SP-B) is essential for the maintenance of biophysical properties and physiological function of pulmonary surfactant. SP-B mRNA is expressed in a cell type-restricted manner in alveolar type II and bronchiolar (Clara) epithelial cells
more » ... of the lung and is developmentally induced. In NCI-H441 cells, a lung cell line with characteristics of Clara cells, a minimal promoter region comprising Ϫ236 to ϩ39 nucleotides supports high-level expression of chloramphenicol acetyltransferase reporter activity. In the present investigation, we characterized the upstream promoter region, Ϫ236 to Ϫ140 nucleotides, that is essential for promoter activity. Deletion mapping identified two segments, Ϫ236 to Ϫ170 and Ϫ170 to Ϫ140 nucleotides, that are important for promoter activity. Mutational analysis and gel mobility shift experiments identified thyroid transcription factor-1, Sp1, and Sp3 as important trans-acting factors that bind to sequences in the upstream promoter region. Our data suggest that SP-B promoter activity is dependent on interactions between factors bound to upstream and downstream regions of the promoter.
doi:10.1152/ajplung.2000.278.3.l477 pmid:10710519 fatcat:egysgqhq2jbkjl5yrnhn5gtub4