The first intron of the human osteopontin gene contains a C/EBP-beta-responsive enhancer

Francesca Giacopelli, Nadia Rosatto, Maria Teresa Divizia, Roberto Cusano, Gianluca Caridi, Roberto Ravazzolo

Research output: Contribution to journalArticle

Abstract

The osteopontin (OPN) protein is found expressed at high level in several processes including fibrotic evolution of organ injuries, tumorigenesis, and immune response. The molecular mechanisms that underly overexpression, especially at the transcriptional level, have been only partially clarified. Therefore, this study was undertaken in search for additional DNA elements in the regulatory regions of the OPN gene and cognate transcription factors. Our results on the region upstream of the transcription start site confirmed that essential elements are located within the first 100 bp. Analysis of the sequence that includes the first untranslated exon and first intron revealed that it could enhance the promoter activity. Experiments of transfection of constructs containing different fragments of this sequence showed that most of the enhancer activity was confined in the terminal 30-bp tract of the first intron, although it was not functioning in a myofibroblast cell line. DNA/protein binding assays and cotransfection experiments showed that the C/EBP-beta transcription factor was able to bind a recognition sequence in this 30-bp segment. We found a bi-allelic sequence polymorphism at +245 in the first intron, which did not show a significant functional effect, but is a useful tool for future association studies.

Original languageEnglish
Pages (from-to)95-104
Number of pages10
JournalGene Expression
Volume11
Issue number2
Publication statusPublished - 2003

Keywords

  • C/EBP-beta
  • Enhancer
  • Osteopontin
  • Transcription

ASJC Scopus subject areas

  • Genetics

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