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dc.contributor.authorPfenning, Andreas R.
dc.contributor.authorSpotts, James M.
dc.contributor.authorSu, Dan
dc.contributor.authorWest, Anne E.
dc.contributor.authorNitabach, Michael N.
dc.contributor.authorKim, Tae-Hyun
dc.contributor.authorHemberg, Martin
dc.date.accessioned2011-04-08T15:42:30Z
dc.date.issued2010
dc.identifier.citationPfenning, Andreas R., Tae-Kyung Kim, James M. Spotts, Martin Hemberg, Dan Su, and Anne E. West. 2010. Genome-wide identification of Calcium-Response Factor (CaRF) binding sites predicts a role in regulation of neuronal signaling pathways. PLoS ONE 5(5).en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4817512
dc.description.abstractCalcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no homology with other transcription factors, its properties and gene targets have remained unknown. Here we show that the DNA binding domain of CaRF has been highly conserved across evolution and that CaRF binds DNA directly in a sequence-specific manner in the absence of other eukaryotic cofactors. Using a binding site selection screen we identify a high-affinity consensus CaRF response element (cCaRE) that shares significant homology with the CaRE1 element of Bdnf. In a genome-wide chromatin immunoprecipitation analysis (ChIP-Seq), we identified 176 sites of CaRF-specific binding (peaks) in neuronal genomic DNA. 128 of these peaks are within 10kB of an annotated gene, and 60 are within 1kB of an annotated transcriptional start site. At least 138 of the CaRF peaks contain a common 10-bp motif with strong statistical similarity to the cCaRE, and we provide evidence predicting that CaRF can bind independently to at least 64.5% of these motifs in vitro. Analysis of this set of putative CaRF targets suggests the enrichment of genes that regulate intracellular signaling cascades. Finally we demonstrate that expression of a subset of these target genes is altered in the cortex of Carf knockout (KO) mice. Together these data strongly support the characterization of CaRF as a unique transcription factor and provide the first insight into the program of CaRF-regulated transcription in neurons.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0010870en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877716/pdf/en_US
dash.licenseLAA
dc.subjectneuroscienceen_US
dc.subjectbiochemistryen_US
dc.subjecttranscription and translationen_US
dc.subjectcell biologyen_US
dc.subjectneuronal signaling mechanismsen_US
dc.titleGenome-Wide Identification of Calcium-Response Factor (CaRF) Binding Sites Predicts a Role in Regulation of Neuronal Signaling Pathwaysen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorKim, Tae-Hyun
dc.date.available2011-04-08T15:42:30Z
dash.affiliation.otherHMS^Microbiology and Molecular Geneticsen_US
dc.identifier.doi10.1371/journal.pone.0010870*
dash.authorsorderedfalse
dash.contributor.affiliatedKim, Tae-Hyun
dash.contributor.affiliatedHemberg, Martin


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