Discovery of transcriptional programs in cerebral ischemia by in silico promoter analysis

Dirk A. Ridder, Svetlana Bulashevska, Ganta Vijay Chaitanya, Phanithi Prakash Babu, Benedikt Brors, Roland Eils, Armin Schneider, Markus Schwaninger

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 β (C/EBPβ) and vitamin D receptor (VDR), are activated as predicted. Immunohistochemistry demonstrated that C/EBPβ and VDR translocated to the nucleus in cerebral ischemia. Chromatin immunoprecipitation revealed increased binding of C/EBPβ 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/EBPβ 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.

Original languageEnglish (US)
Pages (from-to)3-13
Number of pages11
JournalBrain Research
Volume1272
DOIs
StatePublished - May 26 2009
Externally publishedYes

Keywords

  • Bioinformatics
  • C/EBPβ
  • Cerebral ischemia
  • Promoter
  • Transcription
  • Vitamin D receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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