Molecular cloning and characterization of a transcription factor for the C-type natriuretic peptide gene promoter

Eur J Biochem. 1996 Dec 15;242(3):460-6. doi: 10.1111/j.1432-1033.1996.460rr.x.


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.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cloning, Molecular
  • Cytokines / pharmacology
  • DNA-Binding Proteins / genetics
  • Gene Expression
  • Gene Expression Regulation
  • Humans
  • Molecular Sequence Data
  • Natriuretic Peptide, C-Type
  • Promoter Regions, Genetic
  • Proteins / genetics*
  • Rats
  • Repressor Proteins*
  • Tissue Distribution
  • Transcription Factors / genetics*
  • Transforming Growth Factor beta / pharmacology


  • Cytokines
  • DNA-Binding Proteins
  • Proteins
  • Repressor Proteins
  • TSC22D1 protein, human
  • Transcription Factors
  • Transforming Growth Factor beta
  • Tsc22d1 protein, rat
  • Natriuretic Peptide, C-Type

Associated data

  • GENBANK/D38585