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.
%0 Journal Article
%1 ridder2009discovery
%A Ridder, Dirk A.
%A Bulashevska, Svetlana
%A Chaitanya, Ganta Vijay
%A Babu, Phanithi Prakash
%A Brors, Benedikt
%A Eils, Roland
%A Schneider, Armin
%A Schwaninger, Markus
%D 2009
%J Brain Res
%K Activation; Analysis; Animal; Animals; Binding Biology, Brain C57BL; CCAAT-Enhancer-Binding Calcitriol, Cerebral Chromatin Computational Cortex, Disease Female; Genetic; Humans; Immunoprecipitation, Inbred Ischemia, Logistic Male; Mice, Mice; Microarray Models, Models; Molecular; Promoter Protein-beta, Receptors, Regions, Sites, Transcriptional Up-Regulation, genetics/pathology/physiopathology; genetics; metabolism; methods; physiology
%P 3--13
%R 10.1016/j.brainres.2009.03.046
%T Discovery of transcriptional programs in cerebral ischemia by in silico promoter analysis.
%U http://dx.doi.org/10.1016/j.brainres.2009.03.046
%V 1272
%X 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.
@article{ridder2009discovery,
__markedentry = {[bbrors:6]},
abstract = {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.},
added-at = {2015-04-09T12:36:21.000+0200},
author = {Ridder, Dirk A. and Bulashevska, Svetlana and Chaitanya, Ganta Vijay and Babu, Phanithi Prakash and Brors, Benedikt and Eils, Roland and Schneider, Armin and Schwaninger, Markus},
biburl = {https://www.bibsonomy.org/bibtex/2377c8b90ac46351deb49649997f59a37/bbrors},
doi = {10.1016/j.brainres.2009.03.046},
institution = {Department of Pharmacology, University of Heidelberg, Germany.},
interhash = {b9676d40a8a7832f1e8f1608080d6598},
intrahash = {377c8b90ac46351deb49649997f59a37},
journal = {Brain Res},
keywords = {Activation; Analysis; Animal; Animals; Binding Biology, Brain C57BL; CCAAT-Enhancer-Binding Calcitriol, Cerebral Chromatin Computational Cortex, Disease Female; Genetic; Humans; Immunoprecipitation, Inbred Ischemia, Logistic Male; Mice, Mice; Microarray Models, Models; Molecular; Promoter Protein-beta, Receptors, Regions, Sites, Transcriptional Up-Regulation, genetics/pathology/physiopathology; genetics; metabolism; methods; physiology},
language = {eng},
medline-pst = {ppublish},
month = May,
owner = {bbrors},
pages = {3--13},
pii = {S0006-8993(09)00615-5},
pmid = {19344698},
timestamp = {2015-04-09T12:36:21.000+0200},
title = {Discovery of transcriptional programs in cerebral ischemia by in silico promoter analysis.},
url = {http://dx.doi.org/10.1016/j.brainres.2009.03.046},
volume = 1272,
year = 2009
}