DREAM Controls the On/Off Switch of Specific Activity-Dependent Transcription Pathways

Research output: Contribution to journalArticle

Authors

  • 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
  • Tim V P Bliss
  • Mara Dierssen
  • Jose R Naranjo

External organisations

  • National Center of Biotechnology, CSIC and CIBERNED, Madrid, Spain.

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.

Details

Original languageEnglish
Pages (from-to)877-87
Number of pages11
JournalMolecular and Cellular Biology
Volume34
Issue number5
Publication statusPublished - Mar 2014