c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model

J Mol Histol. 2018 Apr;49(2):147-155. doi: 10.1007/s10735-018-9754-7. Epub 2018 Jan 12.


The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

Keywords: Congenital hypothyroidism; EphA5; Hippocampus; Transcription factor; c-Fos.

MeSH terms

  • Animals
  • Congenital Hypothyroidism / metabolism*
  • Gene Expression Regulation
  • Hippocampus / metabolism
  • Neurons / metabolism
  • PC12 Cells
  • Protein Binding
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Receptor, EphA5 / metabolism*
  • Regulatory Elements, Transcriptional


  • Proto-Oncogene Proteins c-fos
  • Epha5 protein, rat
  • Receptor, EphA5