Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection

Steven W. Flavell, Tae Kyung Kim, Jesse M. Gray, David A. Harmin, Martin Hemberg, Elizabeth J. Hong, Eirene Markenscoff-Papadimitriou, Daniel M. Bear, Michael E. Greenberg

Research output: Contribution to journalArticle

292 Scopus citations

Abstract

Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development.

Original languageEnglish (US)
Pages (from-to)1022-1038
Number of pages17
JournalNeuron
Volume60
Issue number6
DOIs
StatePublished - Dec 26 2008

Keywords

  • DNA
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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    Flavell, S. W., Kim, T. K., Gray, J. M., Harmin, D. A., Hemberg, M., Hong, E. J., Markenscoff-Papadimitriou, E., Bear, D. M., & Greenberg, M. E. (2008). Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection. Neuron, 60(6), 1022-1038. https://doi.org/10.1016/j.neuron.2008.11.029