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

Flavell, Steven W. and Kim, Tae-Kyung and Gray, Jesse M. and Harmin, David A. and Hemberg, Martin and Hong, Elizabeth J. and Markenscoff-Papadimitriou, Eirene and Bear, Daniel M. and Greenberg, Michael E. (2008) Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection. Neuron, 60 (6). pp. 1022-1038. ISSN 0896-6273. PMCID PMC2630178. http://resolver.caltech.edu/CaltechAUTHORS:20151005-154745989

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.neuron.2008.11.029DOIArticle
http://www.sciencedirect.com/science/article/pii/S0896627308010507PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630178/PubMed CentralArticle
Additional Information:© 2008 Elsevier. Accepted: November 13, 2008. Published: December 24, 2008. We thank members of the Greenberg lab for their helpful suggestions and discussions and for critical reading of the manuscript. In particular, we thank J. Zieg for assistance with figures and S. Vasquez for preparing primary neuronal cell cultures. We thank the Molecular Genetics Core Facility at Children's Hospital Boston for assistance with microarrays. We also thank Soren Impey and Richard H. Goodman for their early guidance concerning genome-wide applications of ChIP and Gabriel Kreiman for bioinformatics help. M.E.G. acknowledges the generous support of the Nancy Lurie Marks Family Foundation and the generous support of the F.M. Kirby Foundation to the F.M. Kirby Neurobiology Center of Children's Hospital Boston. This work was supported by a Jane Coffin Childs Memorial Fund postdoctoral fellowship (T.K.K), a Lefler postdoctoral fellowship (T.K.K.), a Helen Hay Whitney postdoctoral fellowship (J.M.G.), a National Library of Medicine training fellowship in Biomedical Informatics (D.A.H.), Developmental Disability Research Center grant HD18655 and National Institutes of Health grant NS028829 (M.E.G.).
Funders:
Funding AgencyGrant Number
Nancy Lurie Marks Family FoundationUNSPECIFIED
F. M. Kirby FoundationUNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Lefler postdoctoral fellowshipUNSPECIFIED
Helen Hay Whitney FoundationUNSPECIFIED
National Library of Medicine training fellowshipUNSPECIFIED
NIHHD18655
NIHNS028829
Subject Keywords:MOLNEURO; DNA; SIGNALING
PubMed Central ID:PMC2630178
Record Number:CaltechAUTHORS:20151005-154745989
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20151005-154745989
Official Citation: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, Genome-Wide Analysis of MEF2 Transcriptional Program Reveals Synaptic Target Genes and Neuronal Activity-Dependent Polyadenylation Site Selection, Neuron, Volume 60, Issue 6, 26 December 2008, Pages 1022-1038, ISSN 0896-6273, http://dx.doi.org/10.1016/j.neuron.2008.11.029. (http://www.sciencedirect.com/science/article/pii/S0896627308010507)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:60784
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:06 Oct 2015 15:20
Last Modified:19 Nov 2015 00:43

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