DREAM controls the on/off switch of specific activity-dependent transcription pathways

Mellström, Britt; Sahún, Ignasi; Ruiz Nuño, Ana; Murtra, Patricia; Gómez Villafuertes, Rosa; Savignac, Magalí; Oliveros, Juan C.; González, Paz; Kastanauskaite, Asta; Knafo, Shira; Zhuo, Min; Higuera Matas, Alejandro; Errington, Michael L.; Maldonado, Rafael, 1961-; De Felipe, Javier; Jefferys, John G.R.; Bliss, Tim V. P.; Dierssen, Mara; Naranjo, José R.

DREAM controls the on/off switch of specific activity-dependent transcription pathways

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dc.contributor.author Mellström, Brittca
dc.contributor.author Sahún, Ignasica
dc.contributor.author Ruiz Nuño, Anaca
dc.contributor.author Murtra, Patriciaca
dc.contributor.author Gómez Villafuertes, Rosaca
dc.contributor.author Savignac, Magalíca
dc.contributor.author Oliveros, Juan C.ca
dc.contributor.author González, Pazca
dc.contributor.author Kastanauskaite, Astaca
dc.contributor.author Knafo, Shiraca
dc.contributor.author Zhuo, Minca
dc.contributor.author Higuera Matas, Alejandroca
dc.contributor.author Errington, Michael L.ca
dc.contributor.author Maldonado, Rafael, 1961-ca
dc.contributor.author De Felipe, Javierca
dc.contributor.author Jefferys, John G.R.ca
dc.contributor.author Bliss, Tim V. P.ca
dc.contributor.author Dierssen, Maraca
dc.contributor.author Naranjo, José R.ca
dc.date.accessioned 2015-03-23T08:49:18Z
dc.date.available 2015-03-23T08:49:18Z
dc.date.issued 2014ca
dc.description.abstract Changes in nuclear Ca(2+) homeostasis activate specific gene expression programs and are central to the acquisition and storage of information in the brain. DREAM (downstream regulatory element antagonist modulator), also known as calsenilin/KChIP-3 (K(+) channel interacting protein 3), is a Ca(2+)-binding protein that binds DNA and represses transcription in a Ca(2+)-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca(2+)-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). Using genome-wide analysis, we show that DREAM regulates the expression of specific activity-dependent transcription factors in the hippocampus, including Npas4, Nr4a1, Mef2c, JunB, and c-Fos. Furthermore, DREAM regulates its own expression, establishing an autoinhibitory feedback loop to terminate activity-dependent transcription. Ablation of DREAM does not modify activity-dependent transcription because of gene compensation by the other KChIP family members. The expression of daDREAM in the forebrain resulted in a complex phenotype characterized by loss of recurrent inhibition and enhanced long-term potentiation (LTP) in the dentate gyrus and impaired learning and memory. Our results indicate that DREAM is a major master switch transcription factor that regulates the on/off status of specific activity-dependent gene expression programs that control synaptic plasticity, learning, and memory.
dc.description.sponsorship This work was supported by grants from Spanish Ministry of Health and Science, Madrid Community, La Marató, La Caixa, Reina Sofía and Areces Foundations, the EU 6th Framework Program (NeuroNE, CureFXS), the ERA-NET Program (Neuron and E-Rare), and the Medical Research Council. S.K. has a postdoctoral contract from the Ramón y Cajal Program of the Ministry of Science and Innovation.
dc.format.mimetype application/pdfca
dc.identifier.citation Mellström B, Sahún I, Ruiz-Nuño A, Murtra P, Gomez-Villafuertes R, Savignac M et al. DREAM controls the on/off switch of specific activity-dependent transcription pathways. Mol Cell Biol. 2014 Mar;34(5):877-87. DOI: 10.1128/MCB.00360-13ca
dc.identifier.doi http://dx.doi.org/10.1128/MCB.00360-13
dc.identifier.issn 0270-7306ca
dc.identifier.uri http://hdl.handle.net/10230/23255
dc.language.iso engca
dc.publisher American Society for Microbiologyca
dc.relation.ispartof Molecular and cellular biology. 2014 Mar;34(5):877-87
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.subject.other Proteïnes
dc.subject.other Genètica
dc.subject.other Cervell
dc.title DREAM controls the on/off switch of specific activity-dependent transcription pathwaysca
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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