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 language | English |
|---|---|
| Pages (from-to) | 95-104 |
| Number of pages | 10 |
| Journal | Gene Expression |
| Volume | 11 |
| Issue number | 2 |
| Publication status | Published - 2003 |
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Keywords
- C/EBP-beta
- Enhancer
- Osteopontin
- Transcription
ASJC Scopus subject areas
- Genetics
Cite this
The first intron of the human osteopontin gene contains a C/EBP-beta-responsive enhancer. / Giacopelli, Francesca; Rosatto, Nadia; Divizia, Maria Teresa; Cusano, Roberto; Caridi, Gianluca; Ravazzolo, Roberto.
In: Gene Expression, Vol. 11, No. 2, 2003, p. 95-104.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The first intron of the human osteopontin gene contains a C/EBP-beta-responsive enhancer
AU - Giacopelli, Francesca
AU - Rosatto, Nadia
AU - Divizia, Maria Teresa
AU - Cusano, Roberto
AU - Caridi, Gianluca
AU - Ravazzolo, Roberto
PY - 2003
Y1 - 2003
N2 - 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.
AB - 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.
KW - C/EBP-beta
KW - Enhancer
KW - Osteopontin
KW - Transcription
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M3 - Article
VL - 11
SP - 95
EP - 104
JO - Gene Expression
JF - Gene Expression
SN - 1052-2166
IS - 2
ER -