title: DREAM controls the on/off switch of specific activity-dependent transcription pathways.
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.
authors.affiliation: National Center of Biotechnology, CSIC and CIBERNED, Madrid, Spain.
authors.forename: Britt
authors.initials: B
authors.lastname: Mellström
authors.forename: Ignasi
authors.initials: I
authors.lastname: Sahún
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Nuño
authors.forename: Patricia
authors.initials: P
authors.lastname: Murtra
authors.forename: Rosa
authors.initials: R
authors.lastname: Gomez-Villafuertes
authors.forename: Magali
authors.initials: M
authors.lastname: Savignac
authors.forename: Juan C
authors.initials: JC
authors.lastname: Oliveros
authors.forename: Paz
authors.initials: P
authors.lastname: Gonzalez
authors.forename: Asta
authors.initials: A
authors.lastname: Kastanauskaite
authors.forename: Shira
authors.initials: S
authors.lastname: Knafo
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
authors.forename: Alejandro
authors.initials: A
authors.lastname: Higuera-Matas
authors.forename: Michael L
authors.initials: ML
authors.lastname: Errington
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Javier
authors.initials: J
authors.lastname: DeFelipe
authors.forename: John G R
authors.initials: JG
authors.lastname: Jefferys
authors.forename: Tim V P
authors.initials: TV
authors.lastname: Bliss
authors.forename: Mara
authors.initials: M
authors.lastname: Dierssen
authors.forename: Jose R
authors.initials: JR
authors.lastname: Naranjo
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D059330:GABAergic Neurons / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D051605:Kv Channel-Interacting Proteins / Q000235:genetics* / Q000378:metabolism*; D007858:Learning; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D016548:Prosencephalon / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002118:Calcium; D017362:Cyclic AMP Response Element-Binding Protein; D051605:Kv Channel-Interacting Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C492004:Creb1 protein, mouse; C496756:Csen protein, mouse; C533005:Npas4 protein, mouse