Modulation of epidermal growth factor receptor gene transcription by a polymorphic dinucleotide repeat in intron 1

The influence of a highly polymorphic CA dinucleotide repeat in the epiderm al growth factor receptor (EGFR) gene on transcription was examined with a quantitative nuclear run-off method. We could demonstrate that transcriptio n of the EG;FR gene is inhibited by approximately 80% in alleles with 21 CA repeats. In experiments with polymerase chain reaction products that spann ed a region of more than 4,000 base pairs and contained the promoter, two e nhancers, and the polymorphic region in the first intron of the gene, we fo und that transcription activity declines with increasing numbers of CA dinu cleotides. In vivo pre-mRNA expression data from cultured cell, lines suppo rt these findings, although other regulation mechanisms can outweigh this e ffect. In addition, we showed that under our experimental conditions RNA el ongation terminates at a site closely downstream of the simple sequence rep eat and that there are two separate major transcription start sites. Our re sults provide new insights in individually different EGFR gene expression a nd the role of the CA repeat in transcription of this proto-oncogene.