Modulation of transcription of the platelet-derived growth factor A-chain gene by a promoter region sensitive to S1 nuclease.
J Biol Chem
; 267(24): 17022-31, 1992 Aug 25.
Article
em En
| MEDLINE
| ID: mdl-1512241
ABSTRACT
Homodimers of the platelet-derived growth factor (PDGF) A-chain are strong mitogens for cells of mesenchymal origin. Differences in the levels of expression of the PDGF A-chain gene have been reported in both normal and transformed cell lines, suggesting that transcription of the PDGF A-chain gene is highly regulated. We have now identified two S1-hypersensitive sites which flank a 13-base pair oligo(dG).oligo(dC) sequence located 70-82 base pairs upstream of the transcription initiation site. Three lines of evidence suggest that these S1-sensitive sites contribute to optimum promoter activity. Nuclear protein(s) binding to these sites were detected in gel mobility shift assays. Deletion of the S1-sensitive sites results in a 2-3-fold decrease in the transcriptional activity and eliminated sensitivity to S1 nuclease. Deletions in the oligo(dG).oligo(dC) motif also eliminated sensitivity to S1 and resulted in a 2.5-fold decrease of the promoter activity in the stable transfection assays. The results suggest that the highly G+C-rich region in the PDGF A-chain gene promoter locally induces the formation of non-B-form DNA under torsional stress which appears to be important in the transcriptional regulation of the PDGF A-chain gene in vivo.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Fator de Crescimento Derivado de Plaquetas
/
Endonucleases Específicas para DNA e RNA de Cadeia Simples
/
Regiões Promotoras Genéticas
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article