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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
34
|
| pubmed:dateCreated |
1994-1-4
|
| pubmed:databankReference | |
| pubmed:abstractText |
The serum concentration of rat T1 kininogen increases 20-30-fold in response to acute inflammation. This increase, induced in the liver, is regulated primarily at the transcriptional level. In contrast, synthesis of a homologous K kininogen is not induced. In this study, we further analyzed a 321-base pair interleukin (IL)-6 response element in the T1 kininogen promoter and showed that it consists of at least three functionally distinct sequences (A, B, and C boxes). All three sequences were required for full promoter activity. The B box, a strong C/EBP-binding site, was crucial for T1 kininogen's basal expression, whereas A and C boxes resembled the type II IL-6 response elements and were critical for the cytokine response. C/EBP alpha, -beta, and -delta interacted with the B box sequence; however, upon IL-6 stimulation, C/EBP delta binding activity was dramatically induced and became the predominant factor binding to this site. Consistent with these binding studies were the cotransfection experiments, revealing that C/EBP delta was the most potent transactivator under induced conditions and that its transactivation on the T1 kininogen promoter required an intact B box. These findings substantiated the importance of the B box in eliciting the full acute-phase response. A sequence comparison showed the K kininogen promoter contained identical A and B boxes but differed from the T1 kininogen promoter by two nucleotides at the C box. This divergence reduced the IL-6 response by approximately 4-fold, thus contributing to the differential inflammatory response. Our studies demonstrate that evolutionary divergence of a few nucleotides at a critical sequence in the promoter regions can profoundly alter the expression patterns of downstream genes.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Protein-delta,
http://linkedlifedata.com/resource/pubmed/chemical/CCAAT-Enhancer-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/CEBPD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cebpd protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Kininogens,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
268
|
| pubmed:geneSymbol |
T1K
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
25311-9
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8244962-Animals,
pubmed-meshheading:8244962-Base Sequence,
pubmed-meshheading:8244962-Binding Sites,
pubmed-meshheading:8244962-CCAAT-Enhancer-Binding Protein-delta,
pubmed-meshheading:8244962-CCAAT-Enhancer-Binding Proteins,
pubmed-meshheading:8244962-Cell Line,
pubmed-meshheading:8244962-DNA-Binding Proteins,
pubmed-meshheading:8244962-Dexamethasone,
pubmed-meshheading:8244962-Exons,
pubmed-meshheading:8244962-Gene Expression Regulation,
pubmed-meshheading:8244962-Humans,
pubmed-meshheading:8244962-Interleukin-6,
pubmed-meshheading:8244962-Kininogens,
pubmed-meshheading:8244962-Molecular Sequence Data,
pubmed-meshheading:8244962-Nuclear Proteins,
pubmed-meshheading:8244962-Oligodeoxyribonucleotides,
pubmed-meshheading:8244962-Promoter Regions, Genetic,
pubmed-meshheading:8244962-Rats,
pubmed-meshheading:8244962-Recombinant Proteins,
pubmed-meshheading:8244962-Transcription, Genetic,
pubmed-meshheading:8244962-Transcription Factors,
pubmed-meshheading:8244962-Transfection,
pubmed-meshheading:8244962-Tumor Cells, Cultured
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Differential acute-phase response of rat kininogen genes involves type I and type II interleukin-6 response elements.
|
| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|