Intronic enhancer region governs transcript-specific <i>Bdnf</i> expression in rodent neurons.

Abstract

Brain-derived neurotrophic factor (BDNF) controls the survival, growth, and function of neurons both during the development and in the adult nervous system. <i>Bdnf</i> is transcribed from several distinct promoters generating transcripts with alternative 5' exons. <i>Bdnf</i> 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 <i>Bdnf</i> gene that regulates both basal and stimulus-dependent expression of the <i>Bdnf</i> 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 <i>Bdnf</i> 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.