Source:http://linkedlifedata.com/resource/pubmed/id/15118068
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
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| pubmed:dateCreated |
2004-6-28
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| pubmed:abstractText |
To unravel the mechanisms that regulate the human secretin gene expression, in this study, we have used secretin-expressing (HuTu-80 cells, human duodenal adenocarcinoma) and non-secretin-expressing [PANC-1 (human pancreatic ductile carcinoma) and HepG2 (human hepatocellular carcinoma) cells] cell models for in vitro and in vivo analyses. By transient transfection assays, within the promoter region (-11 to -341 from ATG, relative to the ATG initiation codon), we have initially identified several functional motifs including an E-box and 2 GC-boxes. Results from gel mobility shift and chromatin immunoprecipitation assays confirmed further that NeuroD, E2A, Sp1, and Sp3 bind to these E- and GC-boxes in HuTu-80 cells in vitro and in vivo, whereas only high levels of Sp3 is observed to bind the promoter in HepG2 cells. In addition, overexpression of Sp3 resulted in a dose-dependent repression of the Sp1-mediated transactivation. Collectively, these data suggest that the Sp1/Sp3 ratio is instrumental to controlling secretin gene expression in secretin-producing and non-secretin-producing cells. The functions of GC-box and Sp proteins prompted us to investigate the possible involvement of DNA methylation in regulating this gene. Consistent with this idea, we found a putative CpG island (-336 to 262 from ATG) that overlaps with the human secretin gene promoter. By methylation-specific PCR, all the CpG dinucleo-tides (26 of them) within the CpG island in HuTu-80 cells are unmethylated, whereas all these sites are methylated in PANC-1 and HepG2 cells. The expressions of secretin in PANC-1 and HepG2 cells were subsequently found to be significantly activated by a demethylation agent, 5'-Aza-2' deoxycytidine. Taken together, our data indicate that the human secretin gene is controlled by the in vivo Sp1/Sp3 ratio and the methylation status of the promoter.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxycytidine,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NeuroD protein,
http://linkedlifedata.com/resource/pubmed/chemical/Plicamycin,
http://linkedlifedata.com/resource/pubmed/chemical/SP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Secretin,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Sp3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TCF3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0888-8809
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
18
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1740-55
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:15118068-5' Flanking Region,
pubmed-meshheading:15118068-Animals,
pubmed-meshheading:15118068-Base Sequence,
pubmed-meshheading:15118068-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:15118068-CpG Islands,
pubmed-meshheading:15118068-DNA Methylation,
pubmed-meshheading:15118068-DNA-Binding Proteins,
pubmed-meshheading:15118068-Deoxycytidine,
pubmed-meshheading:15118068-Drosophila,
pubmed-meshheading:15118068-E-Box Elements,
pubmed-meshheading:15118068-Gene Expression Regulation,
pubmed-meshheading:15118068-Humans,
pubmed-meshheading:15118068-Molecular Sequence Data,
pubmed-meshheading:15118068-Nerve Tissue Proteins,
pubmed-meshheading:15118068-Plicamycin,
pubmed-meshheading:15118068-Promoter Regions, Genetic,
pubmed-meshheading:15118068-Secretin,
pubmed-meshheading:15118068-Sp1 Transcription Factor,
pubmed-meshheading:15118068-Sp3 Transcription Factor,
pubmed-meshheading:15118068-Transcription Factors,
pubmed-meshheading:15118068-Tumor Cells, Cultured
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| pubmed:year |
2004
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| pubmed:articleTitle |
Regulation of the human secretin gene is controlled by the combined effects of CpG methylation, Sp1/Sp3 ratio, and the E-box element.
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| pubmed:affiliation |
Department of Zoology, University of Hong Kong, Pokfulam Road, Hong Kong, People's Republic of China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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