Comparative analysis of cis-regulation following stroke and seizures in subspaces of conserved eigensystems.
BACKGROUND
It is often desirable to separate effects of different regulators on gene expression, or to identify effects of the same regulator across several systems. Here, we focus on the rat brain following stroke or seizures, and demonstrate how the two tasks can be approached simultaneously.


RESULTS
We applied SVD to time-series gene expression datasets from the rat experimental models of stroke and seizures. We demonstrate conservation of two eigensystems, reflecting inflammation and/or apoptosis (eigensystem 2) and neuronal synaptic activity (eigensystem 3), between the stroke and seizures. We analyzed cis-regulation of gene expression in the subspaces of the conserved eigensystems. Bayesian networks analysis was performed separately for either experimental model, with cross-system validation of the highest-ranking features. In this way, we correctly re-discovered the role of AP1 in the regulation of apoptosis, and the involvement of Creb and Egr in the regulation of synaptic activity-related genes. We identified a novel antagonistic effect of the motif recognized by the nuclear matrix attachment region-binding protein Satb1 on AP1-driven transcriptional activation, suggesting a link between chromatin loop structure and gene activation by AP1. The effects of motifs binding Satb1 and Creb on gene expression in brain conform to the assumption of the linear response model of gene regulation. Our data also suggest that numerous enhancers of neuronal-specific genes are important for their responsiveness to the synaptic activity.


CONCLUSIONS
Eigensystems conserved between stroke and seizures separate effects of inflammation/apoptosis and neuronal synaptic activity, exerted by different transcription factors, on gene expression in rat brain.
Dabrowski
Michal
M
Laboratory of Transcription Regulation, Department of Cell Biology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland. m.dabrowski@nencki.gov.pl
Dojer
Norbert
N
Zawadzka
Malgorzata
M
Mieczkowski
Jakub
J
Kaminska
Bozena
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001499:Bayes Theorem; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D053263:Gene Regulatory Networks / Q000502:physiology*; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D046228:Microarray Analysis; D008954:Models, Biological; D051381:Rats; D012044:Regression Analysis; D012640:Seizures / Q000503:physiopathology*; D020521:Stroke / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D036961:Matrix Attachment Region Binding Proteins; D018808:Transcription Factor AP-1