A comparative genomics approach to identifying the plasticity transcriptome.
BACKGROUND
Neuronal activity regulates gene expression to control learning and memory, homeostasis of neuronal function, and pathological disease states such as epilepsy. A great deal of experimental evidence supports the involvement of two particular transcription factors in shaping the genomic response to neuronal activity and mediating plasticity: CREB and zif268 (egr-1, krox24, NGFI-A). The gene targets of these two transcription factors are of considerable interest, since they may help develop hypotheses about how neural activity is coupled to changes in neural function.


RESULTS
We have developed a computational approach for identifying binding sites for these transcription factors within the promoter regions of annotated genes in the mouse, rat, and human genomes. By combining a robust search algorithm to identify discrete binding sites, a comparison of targets across species, and an analysis of binding site locations within promoter regions, we have defined a group of candidate genes that are strong CREB- or zif268 targets and are thus regulated by neural activity. Our analysis revealed that CREB and zif268 share a disproportionate number of targets in common and that these common targets are dominated by transcription factors.


CONCLUSIONS
These observations may enable a more detailed understanding of the regulatory networks that are induced by neural activity and contribute to the plasticity transcriptome. The target genes identified in this study will be a valuable resource for investigators who hope to define the functions of specific genes that underlie activity-dependent changes in neuronal properties.
Pfenning
Andreas R
AR
Department of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA. andreas.pfenning@duke.edu <andreas.pfenning@duke.edu>
Schwartz
Russell
R
Barth
Alison L
AL
D000818:Animals; D001921:Brain / Q000502:physiology*; D050882:CREB-Binding Protein / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D051766:Early Growth Response Protein 1 / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D020543:Proteome / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D009419:Nerve Tissue Proteins; D020543:Proteome; D014157:Transcription Factors; D050882:CREB-Binding Protein