Polymorphisms in the osteopontin promoter affect its transcriptional activity
1 Laboratory of Molecular Genetics G. Gaslini Institute, Genova, Italy 2 Epidemiology and Statistics Unit, G. Gaslini Institute, Genova, Italy 3 Laboratory of Nephrology, G. Gaslini Institute, Genova, Italy 4 Laboratory of Chemical-Clinical Analysis, G. Gaslini Institute, Genova, Italy 5 Department...
Gespeichert in:
| Veröffentlicht in: | Physiological genomics 2004-12, Vol.20 (1), p.87-96 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 96 |
|---|---|
| container_issue | 1 |
| container_start_page | 87 |
| container_title | Physiological genomics |
| container_volume | 20 |
| creator | Giacopelli, Francesca Marciano, Renato Pistorio, Angela Catarsi, Paolo Canini, Silvana Karsenty, Gerard Ravazzolo, Roberto |
| description | 1 Laboratory of Molecular Genetics G. Gaslini Institute, Genova, Italy
2 Epidemiology and Statistics Unit, G. Gaslini Institute, Genova, Italy
3 Laboratory of Nephrology, G. Gaslini Institute, Genova, Italy
4 Laboratory of Chemical-Clinical Analysis, G. Gaslini Institute, Genova, Italy
5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
6 Department of Pediatrics and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at 66, 156, and 443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the 66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the 156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the 443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.
haplotype; gene regulation; Sp1; RUNX2 |
| doi_str_mv | 10.1152/physiolgenomics.00138.2004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_67179423</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67179423</sourcerecordid><originalsourceid>FETCH-LOGICAL-c512t-104ee0d667f3c80906358f4b8e69a249e32dc071d3d3ca53a733ee7244f7e1433</originalsourceid><addsrcrecordid>eNqFkF9r2zAUxcVYWdpsX6GYPezNqf5a9h4GozRtIWV7SJ-FIl_HGrblSUo3f_uqTUohUPp074XfOedyEPpK8IIQQS_GdgrWdVsYXG9NWGBMWLmgGPMP6JQIRnJKC_kx7bjieck4maGzEP4kjstSfEIzIrisSlGdorvfrpt658fWhj5kdshiC5kLEdzohpju0bveRfCZbhowMbMxZNHrIRhvx2jdoLtMm2gfbJw-o5NGdwG-HOYc3S-v1pc3-erX9e3lz1VuBKExJ5gD4LooZMNMiStcMFE2fFNCUWnKK2C0NliSmtXMaMG0ZAxAUs4bCYQzNkff9r7pub87CFH1NhjoOj2A2wVVSCIrTt8HiZSSFVIk8PseNN6F4KFRo7e99pMiWD21ro5aV8-tq6fWk_j8kLLb9FC_Sg81J-DHHmjttv1nPby4ue2klruuW8P_eJxAU7AqpRrrJhnQtw2OPzsI2SNwca91</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17773675</pqid></control><display><type>article</type><title>Polymorphisms in the osteopontin promoter affect its transcriptional activity</title><source>MEDLINE</source><source>American Physiological Society</source><source>Free E-Journal (出版社公開部分のみ）</source><creator>Giacopelli, Francesca ; Marciano, Renato ; Pistorio, Angela ; Catarsi, Paolo ; Canini, Silvana ; Karsenty, Gerard ; Ravazzolo, Roberto</creator><creatorcontrib>Giacopelli, Francesca ; Marciano, Renato ; Pistorio, Angela ; Catarsi, Paolo ; Canini, Silvana ; Karsenty, Gerard ; Ravazzolo, Roberto</creatorcontrib><description>1 Laboratory of Molecular Genetics G. Gaslini Institute, Genova, Italy
2 Epidemiology and Statistics Unit, G. Gaslini Institute, Genova, Italy
3 Laboratory of Nephrology, G. Gaslini Institute, Genova, Italy
4 Laboratory of Chemical-Clinical Analysis, G. Gaslini Institute, Genova, Italy
5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
6 Department of Pediatrics and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at 66, 156, and 443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the 66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the 156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the 443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.
haplotype; gene regulation; Sp1; RUNX2</description><identifier>ISSN: 1094-8341</identifier><identifier>EISSN: 1531-2267</identifier><identifier>DOI: 10.1152/physiolgenomics.00138.2004</identifier><identifier>PMID: 15479859</identifier><language>eng</language><publisher>United States: Am Physiological Soc</publisher><subject>Alleles ; Animals ; Base Sequence ; Binding Sites ; Cell Line ; Cercopithecus aethiops ; Core Binding Factor Alpha 1 Subunit - metabolism ; COS Cells ; DNA Primers - chemistry ; Gene Expression Regulation ; Genes, Reporter ; Genetic Vectors ; Haplotypes ; HeLa Cells ; Humans ; Introns ; Linkage Disequilibrium ; Luciferases - metabolism ; Mice ; Mice, Knockout ; Models, Genetic ; Molecular Sequence Data ; Neoplasm Metastasis ; Osteopontin ; Plasmids - metabolism ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Protein Binding ; Sequence Homology, Nucleic Acid ; Sialoglycoproteins - genetics ; Sp1 Transcription Factor - metabolism ; Transcription, Genetic ; Transfection</subject><ispartof>Physiological genomics, 2004-12, Vol.20 (1), p.87-96</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c512t-104ee0d667f3c80906358f4b8e69a249e32dc071d3d3ca53a733ee7244f7e1433</citedby><cites>FETCH-LOGICAL-c512t-104ee0d667f3c80906358f4b8e69a249e32dc071d3d3ca53a733ee7244f7e1433</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3026,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15479859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Giacopelli, Francesca</creatorcontrib><creatorcontrib>Marciano, Renato</creatorcontrib><creatorcontrib>Pistorio, Angela</creatorcontrib><creatorcontrib>Catarsi, Paolo</creatorcontrib><creatorcontrib>Canini, Silvana</creatorcontrib><creatorcontrib>Karsenty, Gerard</creatorcontrib><creatorcontrib>Ravazzolo, Roberto</creatorcontrib><title>Polymorphisms in the osteopontin promoter affect its transcriptional activity</title><title>Physiological genomics</title><addtitle>Physiol Genomics</addtitle><description>1 Laboratory of Molecular Genetics G. Gaslini Institute, Genova, Italy
2 Epidemiology and Statistics Unit, G. Gaslini Institute, Genova, Italy
3 Laboratory of Nephrology, G. Gaslini Institute, Genova, Italy
4 Laboratory of Chemical-Clinical Analysis, G. Gaslini Institute, Genova, Italy
5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
6 Department of Pediatrics and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at 66, 156, and 443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the 66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the 156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the 443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.
haplotype; gene regulation; Sp1; RUNX2</description><subject>Alleles</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Binding Sites</subject><subject>Cell Line</subject><subject>Cercopithecus aethiops</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>COS Cells</subject><subject>DNA Primers - chemistry</subject><subject>Gene Expression Regulation</subject><subject>Genes, Reporter</subject><subject>Genetic Vectors</subject><subject>Haplotypes</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Introns</subject><subject>Linkage Disequilibrium</subject><subject>Luciferases - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Models, Genetic</subject><subject>Molecular Sequence Data</subject><subject>Neoplasm Metastasis</subject><subject>Osteopontin</subject><subject>Plasmids - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Sequence Homology, Nucleic Acid</subject><subject>Sialoglycoproteins - genetics</subject><subject>Sp1 Transcription Factor - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transfection</subject><issn>1094-8341</issn><issn>1531-2267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF9r2zAUxcVYWdpsX6GYPezNqf5a9h4GozRtIWV7SJ-FIl_HGrblSUo3f_uqTUohUPp074XfOedyEPpK8IIQQS_GdgrWdVsYXG9NWGBMWLmgGPMP6JQIRnJKC_kx7bjieck4maGzEP4kjstSfEIzIrisSlGdorvfrpt658fWhj5kdshiC5kLEdzohpju0bveRfCZbhowMbMxZNHrIRhvx2jdoLtMm2gfbJw-o5NGdwG-HOYc3S-v1pc3-erX9e3lz1VuBKExJ5gD4LooZMNMiStcMFE2fFNCUWnKK2C0NliSmtXMaMG0ZAxAUs4bCYQzNkff9r7pub87CFH1NhjoOj2A2wVVSCIrTt8HiZSSFVIk8PseNN6F4KFRo7e99pMiWD21ro5aV8-tq6fWk_j8kLLb9FC_Sg81J-DHHmjttv1nPby4ue2klruuW8P_eJxAU7AqpRrrJhnQtw2OPzsI2SNwca91</recordid><startdate>20041215</startdate><enddate>20041215</enddate><creator>Giacopelli, Francesca</creator><creator>Marciano, Renato</creator><creator>Pistorio, Angela</creator><creator>Catarsi, Paolo</creator><creator>Canini, Silvana</creator><creator>Karsenty, Gerard</creator><creator>Ravazzolo, Roberto</creator><general>Am Physiological Soc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7X8</scope></search><sort><creationdate>20041215</creationdate><title>Polymorphisms in the osteopontin promoter affect its transcriptional activity</title><author>Giacopelli, Francesca ; Marciano, Renato ; Pistorio, Angela ; Catarsi, Paolo ; Canini, Silvana ; Karsenty, Gerard ; Ravazzolo, Roberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-104ee0d667f3c80906358f4b8e69a249e32dc071d3d3ca53a733ee7244f7e1433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Binding Sites</topic><topic>Cell Line</topic><topic>Cercopithecus aethiops</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>COS Cells</topic><topic>DNA Primers - chemistry</topic><topic>Gene Expression Regulation</topic><topic>Genes, Reporter</topic><topic>Genetic Vectors</topic><topic>Haplotypes</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Introns</topic><topic>Linkage Disequilibrium</topic><topic>Luciferases - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Models, Genetic</topic><topic>Molecular Sequence Data</topic><topic>Neoplasm Metastasis</topic><topic>Osteopontin</topic><topic>Plasmids - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>Sequence Homology, Nucleic Acid</topic><topic>Sialoglycoproteins - genetics</topic><topic>Sp1 Transcription Factor - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Giacopelli, Francesca</creatorcontrib><creatorcontrib>Marciano, Renato</creatorcontrib><creatorcontrib>Pistorio, Angela</creatorcontrib><creatorcontrib>Catarsi, Paolo</creatorcontrib><creatorcontrib>Canini, Silvana</creatorcontrib><creatorcontrib>Karsenty, Gerard</creatorcontrib><creatorcontrib>Ravazzolo, Roberto</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Physiological genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Giacopelli, Francesca</au><au>Marciano, Renato</au><au>Pistorio, Angela</au><au>Catarsi, Paolo</au><au>Canini, Silvana</au><au>Karsenty, Gerard</au><au>Ravazzolo, Roberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphisms in the osteopontin promoter affect its transcriptional activity</atitle><jtitle>Physiological genomics</jtitle><addtitle>Physiol Genomics</addtitle><date>2004-12-15</date><risdate>2004</risdate><volume>20</volume><issue>1</issue><spage>87</spage><epage>96</epage><pages>87-96</pages><issn>1094-8341</issn><eissn>1531-2267</eissn><abstract>1 Laboratory of Molecular Genetics G. Gaslini Institute, Genova, Italy
2 Epidemiology and Statistics Unit, G. Gaslini Institute, Genova, Italy
3 Laboratory of Nephrology, G. Gaslini Institute, Genova, Italy
4 Laboratory of Chemical-Clinical Analysis, G. Gaslini Institute, Genova, Italy
5 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
6 Department of Pediatrics and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
Understanding the molecular mechanisms that underlie regulation of transcription of the human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution of organ damage, tumorigenesis and metastasis, and immune response, in which OPN overexpression is observed. With the aim to evaluate variants with functional effect on transcription, we have analyzed the promoter region and focused our investigation on three common variants present in the first 500 bp upstream of the transcription start site. Transfection of constructs carrying the four most frequent haplotypes relative to variants at 66, 156, and 443 fused to the luciferase reporter gene in a panel of different cell lines showed that one haplotype conferred a significantly reduced level of reporter gene expression in all tested cell lines. We describe that the 66 polymorphism modifies the binding affinity for the SP1/SP3 transcription factors, the 156 polymorphism is included in a yet uncharacterized RUNX2 binding site, and the 443 polymorphism causes differential binding of an unknown factor. The finding of differential effects of various combination of variants in haplotypes may contribute to explain data of association studies reported in several already published articles. Future association studies using haplotypes instead of single OPN variants will allow to achieve more accurate results referable to differential expression of OPN in several common diseases, in which OPN is considered a candidate susceptibility gene.
haplotype; gene regulation; Sp1; RUNX2</abstract><cop>United States</cop><pub>Am Physiological Soc</pub><pmid>15479859</pmid><doi>10.1152/physiolgenomics.00138.2004</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1094-8341 |
| ispartof | Physiological genomics, 2004-12, Vol.20 (1), p.87-96 |
| issn | 1094-8341 1531-2267 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67179423 |
| source | MEDLINE; American Physiological Society; Free E-Journal (出版社公開部分のみ） |
| subjects | Alleles Animals Base Sequence Binding Sites Cell Line Cercopithecus aethiops Core Binding Factor Alpha 1 Subunit - metabolism COS Cells DNA Primers - chemistry Gene Expression Regulation Genes, Reporter Genetic Vectors Haplotypes HeLa Cells Humans Introns Linkage Disequilibrium Luciferases - metabolism Mice Mice, Knockout Models, Genetic Molecular Sequence Data Neoplasm Metastasis Osteopontin Plasmids - metabolism Polymerase Chain Reaction Polymorphism, Genetic Polymorphism, Single Nucleotide Promoter Regions, Genetic Protein Binding Sequence Homology, Nucleic Acid Sialoglycoproteins - genetics Sp1 Transcription Factor - metabolism Transcription, Genetic Transfection |
| title | Polymorphisms in the osteopontin promoter affect its transcriptional activity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T15%3A57%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Polymorphisms%20in%20the%20osteopontin%20promoter%20affect%20its%20transcriptional%20activity&rft.jtitle=Physiological%20genomics&rft.au=Giacopelli,%20Francesca&rft.date=2004-12-15&rft.volume=20&rft.issue=1&rft.spage=87&rft.epage=96&rft.pages=87-96&rft.issn=1094-8341&rft.eissn=1531-2267&rft_id=info:doi/10.1152/physiolgenomics.00138.2004&rft_dat=%3Cproquest_pubme%3E67179423%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17773675&rft_id=info:pmid/15479859&rfr_iscdi=true |