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The Journal of Neuroscience, April 1, 2003, 23(7):2572
Upstream Stimulatory Factors Are Mediators of Ca2+-Responsive Transcription in Neurons
Wen G. Chen1, 2, Anne E. West2, Xu Tao2, Gabriel Corfas2, Marilyn N. Szentirmay3, Michèle Sawadogo3, Charles Vinson4, and Michael E. Greenberg1, 2 1 Program in Biological and Biomedical Sciences, Harvard Medical School, and 2 Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, 3 Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and 4 Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892
To identify molecular mechanisms that control activity-dependent gene expression in the CNS, we have characterized the factors that mediate activity-dependent transcription of BDNF promoter III. We report the identification of a Ca2+-responsive E-box element, CaRE2, within BDNF promoter III that binds upstream stimulatory factors 1 and 2 (USF1/2) and show that USFs are required for the activation of CaRE2-dependent transcription from BDNF promoter 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 genes in vivo. These results suggest a new function for the USFs in the regulation of activity-dependent transcription in neurons.
Key words: upstream stimulatory factor; USF1; USF2; activity-dependent transcription; brain-derived neurotrophic factor; BDNF; calcium; neural plasticity; activity-dependent neural development
Copyright © 2003 Society for Neuroscience 0270-6474/03/2372572-10$05.00/0
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