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

Britt Mellström, Ignasi Sahún, Ana Ruiz-Nuño, Patricia Murtra, Rosa Gomez-Villafuertes, Magali Savignac, Juan C. Oliveros, Paz Gonzalez, Asta Kastanauskaite, Shira Knafo, Min Zhuo, Alejandro Higuera-Matas, Michael L. Errington, Rafael Maldonado, Javier DeFelipe, John G.R. Jefferys, Tim V.P. Bliss, Mara Dierssen, Jose R. Naranjo

Research output: Contribution to journalArticlepeer-review


Changes in nuclear Ca2+ 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 Ca2+-binding protein that binds DNA and represses transcription in a Ca2+-dependent manner. To study the function of DREAM in the brain, we used transgenic mice expressing a Ca2+-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 activitydependent gene expression programs that control synaptic plasticity, learning, and memory.

Original languageEnglish
Pages (from-to)877-887
Number of pages11
JournalMolecular and Cellular Biology
Issue number5
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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