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J Biol Chem, Vol. 274, Issue 19, 13176-13180, May 7, 1999
From the The influence of a highly polymorphic CA
dinucleotide repeat in the epidermal growth factor receptor (EGFR) gene
on transcription was examined with a quantitative nuclear run-off
method. We could demonstrate that transcription of the EGFR gene is
inhibited by approximately 80% in alleles with 21 CA repeats. In
experiments with polymerase chain reaction products that spanned a
region of more than 4,000 base pairs and contained the promoter, two enhancers, and the polymorphic region in the first intron of the gene,
we found that transcription activity declines with increasing numbers
of CA dinucleotides. In vivo pre-mRNA expression data from cultured cell lines support these findings, although other regulation mechanisms can outweigh this effect. In addition, we showed
that under our experimental conditions RNA elongation terminates at a
site closely downstream of the simple sequence repeat and that there
are two separate major transcription start sites. Our results provide
new insights in individually different EGFR gene expression and the
role of the CA repeat in transcription of this proto-oncogene.
Modulation of Epidermal Growth Factor Receptor Gene Transcription
by a Polymorphic Dinucleotide Repeat in Intron 1
§,
Institut für Klinische Chemie und
Laboratoriumsmedizin, University of Münster, 48129 Münster,
Germany and the § Institut für Immunologie, University
of Witten/Herdecke, 58448 Witten, Germany
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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