Molecular Cloning and Characterization of a Transcription Factor for the C-Type Natriuretic Peptide Gene Promoter


  • Note. The novel nucleotide sequence presented here has been submitted to the GenBank data bank and is available under accession number D38585.

K. Nagata, Shionogi Research Laboratories, Shionogi & Co., Ltd., 5-12-4 Sagisu. Fukushima-ku, Osaka, Japan 553


Our previous studies on the promoter function of the human C-type natriuretic peptide (CNP) gene revealed the existence of two GC-rich cis elements essential for gene transcription in rat pituitary-derived GH3 cells. To isolate transcription factors that bind to those GC-rich elements, we screened a λZAP cDNA library derived from GH3 cells by Southwestern screening. Several positive clones with specific binding abilities were obtained, and one was identical as TSC-22, a speculated transcriptional modulator stimulated by transforming growth factor β (TGF-β) of unknown function. TSC-22 significantly enhanced CNP promoter activity in GH3 cells. We further cloned a 1.8-kb full-length human TSC-22 cDNA from a fetal kidney cDNA library by a combination of polymerase chain reaction and the rapid amplification of the cDNA ends technique. In adults, human TSC-22 mRNA was highly expressed in brain, lung and heart. TSC-22 gene expression in GH3 and human aortic endothelial cells was stimulated by cytokines including TGF-β in correlation with the CNP mRNA increase. These results suggest that TSC-22 is a transcriptional regulator of the CNP gene and transmits signals from cytokines, such as TGF-β, to CNP gene expression.