Prolonged alteration in E-box binding after a single systemic kainate injection: Potential relation to F1/GAP-43 gene expression

Walter R. Kinney, Robert K. McNamara, Eric Valcourt, Aryeh Routtenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


The presence in hippocampus of a basic helix-loop-helix (bHLH) family of transcription factors (TFs) specifically binding in an electrophoretic mobility shift assay (EMSA) to the E-box recognition element was established by selective blockade of binding both by cold competition and by an antibody to MyoD1, an E-box TF. Protein source was from a micro-dissected preparation enriched in hippocampal granule cells. Specific E-box binding of hippocampal transcription factors was significantly reduced in kainate acid (KA) treated animals. This was observed at 24 and 72 h, but not before (3, 6 h) or after (96 h). This is the first report to our knowledge to study functional regulation of E-box binding protein in adult hippocampus. To determine the generality of this E-box regulatory event, we studied four other situations, in addition to kainate treatment, where axonal growth is known or has been suggested to increase: NGF treatment of PC12 cells, unilateral hilar lesions, long-term potentiation after 1 h, and postnatal rat hippocampal development. In all four cases, decreased E-box binding was observed. The recent link of F1/GAP-43 mRNA induction in hippocampal granule cells by KA to growth of their axons, the messy fibers in the adult rat, suggests a potential role for the F1/GAP-43 5' flanking promoter region in regulating neurite outgrowth. Since in all cases decreased E-box binding preceded increased F1/GAP-43 mRNA expression, it is suggested that E-box binding to the F1/GAP-43 promoter in hippocampal granule cells could negatively regulate F1/GAP-43 gene expression. Indeed, analysis of recognition elements on the F1/GAP-43 gene revealed an arrangement, previously described in other genes, of multiple adjacent E-box elements. E-box binding of bHLH transcription factors is likely to occur on several different genes in addition to F1/GAP-43. It is, therefore, attractive to think that E-box binding is regulated by in vivo activation of the adult brain and that this gene regulatory event participates in the orchestration of molecular and cellular responses underlying axonal growth.

Original languageEnglish (US)
Pages (from-to)25-36
Number of pages12
JournalMolecular Brain Research
Issue number1
StatePublished - May 1996


  • DNA binding
  • Development
  • GAP-43
  • Granule cell
  • Hippocampus
  • Long-term potentiation
  • NGF

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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