An S1 nuclease sensitive region in the PDGFA-chain gene promoter contains a positive transcriptional regulatory element

Abstract

Homodimers of the platelet-derived growth factor (PDGF) A-chain are strong mitogens for cells of mesenchymal origin and appear to be functionally important during development and perhaps in phenotypic transformation. In order to understand mechanisms of the developmental regulation of the PDGF A-chain gene and its dysregulation in transformation, we used S1 nuclease to identify and map an S1 hypersensitive region that is located 482 to 513 base pairs upstream of the transcription initiation site of the PDGF A-chain gene. A single nuclear protein binds to this site in gel mobility shift assays. This site confers a 2-3 fold increase in transcriptional activity when inserted into a heterologous promoter and analysed in transient transfection assays. The results suggest that this region of DNA under torsional stress locally assumes a single stranded character and functions to upregulate promoter activity.