%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 }