Source:http://linkedlifedata.com/resource/pubmed/id/19344698
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:dateCreated |
2009-5-18
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| pubmed:abstractText |
In stroke, gene transcription plays a central role in processes such as neuroinflammation and neuroregeneration. To predict new transcriptional regulatory mechanisms in cerebral ischemia, we applied a computational approach combining two kinds of information: the results of a microarray analysis in a mouse model of stroke and in silico detection of transcription factor (TF) binding sites in promoter regions of the genes on the array. By using a discriminative logistic regression model, we identified binding sites significantly associated with the up-regulation of genes. Out of 356 TF binding sites defined in TRANSFAC, we could link 32 to gene up-regulation in cerebral ischemia. These sites bind both TFs with an established and a so far unknown role in cerebral ischemia. To evaluate the results further we investigated whether two TFs, CCAAT/enhancer binding protein beta (C/EBP beta) and vitamin D receptor (VDR), are activated as predicted. Immunohistochemistry demonstrated that C/EBP beta and VDR translocated to the nucleus in cerebral ischemia. Chromatin immunoprecipitation revealed increased binding of C/EBP beta to the promoter of its target gene saa3. In addition, we found evidence for the up-regulation of VDR in brain samples from human stroke patients. These results confirm the activation of C/EBP beta and VDR in cerebral ischemia. Thus, our in silico analysis may provide additional information on transcriptional regulation in stroke and suggests several novel transcriptional programs for further exploration.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
1872-6240
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
26
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| pubmed:volume |
1272
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3-13
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| pubmed:meshHeading |
pubmed-meshheading:19344698-Animals,
pubmed-meshheading:19344698-Binding Sites,
pubmed-meshheading:19344698-Brain Ischemia,
pubmed-meshheading:19344698-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:19344698-Cerebral Cortex,
pubmed-meshheading:19344698-Chromatin Immunoprecipitation,
pubmed-meshheading:19344698-Computational Biology,
pubmed-meshheading:19344698-Disease Models, Animal,
pubmed-meshheading:19344698-Female,
pubmed-meshheading:19344698-Humans,
pubmed-meshheading:19344698-Logistic Models,
pubmed-meshheading:19344698-Male,
pubmed-meshheading:19344698-Mice,
pubmed-meshheading:19344698-Mice, Inbred C57BL,
pubmed-meshheading:19344698-Microarray Analysis,
pubmed-meshheading:19344698-Models, Molecular,
pubmed-meshheading:19344698-Promoter Regions, Genetic,
pubmed-meshheading:19344698-Receptors, Calcitriol,
pubmed-meshheading:19344698-Transcriptional Activation,
pubmed-meshheading:19344698-Up-Regulation
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| pubmed:year |
2009
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| pubmed:articleTitle |
Discovery of transcriptional programs in cerebral ischemia by in silico promoter analysis.
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| pubmed:affiliation |
Department of Pharmacology, University of Heidelberg, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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