Activity-dependent regulation of gene transcription

Bdnf promoter III activation in response to calcium influx depends on the recruitment of at least three transcriptional activators, including calcium response factor (CaRF), upstream stimulatory factors (USFs), and CREB. These activators are believed to sit on the promoter, poised to receive an activation signal. Additionally, the methyl-DNA binding transcriptional repressor MeCP2 is bound to Bdnf promoter III in resting neurons, and dissociates in response to calcium influx to allow histone acetylation and exon III transcription. Highlighting the importance of this pathway for cognitive development, many of molecular players in the signaling pathway mediating activity-dependent Bdnf induction are mutated in several genetic disorders of cognition, from L-type voltage gated calcium channels at the membrane (Timothy syndrome) to kinases transducing the calcium signal (e.g. Rsk2 in Coffin-Lowry syndrome) to the many transcriptional regulators on this promoter (e.g. MeCP2 in Rett Syndrome). West, AE (2001) Proc Natl Acad Sci 98: 11024.