Intronic enhancer region governs transcript-specific Bdnf expression in rodent neurons

Elife. 2021 Feb 9;10:e65161. doi: 10.7554/eLife.65161.


Brain-derived neurotrophic factor (BDNF) controls the survival, growth, and function of neurons both during the development and in the adult nervous system. Bdnf is transcribed from several distinct promoters generating transcripts with alternative 5' exons. Bdnf transcripts initiated at the first cluster of exons have been associated with the regulation of body weight and various aspects of social behavior, but the mechanisms driving the expression of these transcripts have remained poorly understood. Here, we identify an evolutionarily conserved intronic enhancer region inside the Bdnf gene that regulates both basal and stimulus-dependent expression of the Bdnf transcripts starting from the first cluster of 5' exons in mouse and rat neurons. We further uncover a functional E-box element in the enhancer region, linking the expression of Bdnf and various pro-neural basic helix-loop-helix transcription factors. Collectively, our results shed new light on the cell-type- and stimulus-specific regulation of the important neurotrophic factor BDNF.

Keywords: BDNF; CRISPR; E-box; TCF4; chromosomes; enhancer; gene expression; human; mouse; neurons; neuroscience; rat.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Female
  • Gene Expression Regulation*
  • Humans
  • Introns*
  • Male
  • Mice
  • Neurons / physiology*
  • Promoter Regions, Genetic*
  • Rats
  • Rats, Sprague-Dawley


  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor

Associated data

  • GEO/GSE21161
  • GEO/GSE52386
  • GEO/GSE60192
  • GEO/GSE67539
  • GEO/GSE70872
  • GEO/GSE67482
  • GEO/GSE150589
  • GEO/GSE150499