Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter.
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 lambda ZAP 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 beta (TGF-beta) 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-beta, 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-beta, to CNP gene expression.
Ohta
S
S
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Shimekake
Y
Y
Nagata
K
K
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D016207:Cytokines / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D020098:Natriuretic Peptide, C-Type; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016207:Cytokines; D004268:DNA-Binding Proteins; D011506:Proteins; D012097:Repressor Proteins; C099726:TSC22D1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C490982:Tsc22d1 protein, rat; D020098:Natriuretic Peptide, C-Type