Upstream Stimulatory Factors Are Mediators of Ca2+-Responsive Transcription in Neurons

Abstract
To identify molecular mechanisms that control activity-dependent gene expression in the CNS, we have characterized the factors that mediate activity-dependent transcription ofBDNFpromoter III. We report the identification of a Ca2+-responsive E-box element, CaRE2, withinBDNFpromoter III that binds upstream stimulatory factors 1 and 2 (USF1/2) and show that USFs are required for the activation of CaRE2-dependent transcription fromBDNFpromoter III. We find that the transcriptional activity of the USFs is regulated by Ca2+-activated signaling pathways in neurons and that the USFs bind to the promoters of a number of neuronal activity-regulated genesin vivo. These results suggest a new function for the USFs in the regulation of activity-dependent transcription in neurons.