A comparative genomics approach to identifying the plasticity transcriptome

BMC Neurosci. 2007 Mar 13;8:20. doi: 10.1186/1471-2202-8-20.

Abstract

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Brain / physiology*
  • CREB-Binding Protein / genetics*
  • Chromosome Mapping / methods*
  • Early Growth Response Protein 1 / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics*
  • Neuronal Plasticity / genetics*
  • Proteome / genetics
  • Transcription Factors / genetics*

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Nerve Tissue Proteins
  • Proteome
  • Transcription Factors
  • CREB-Binding Protein