Changes in nuclear Ca2+ homeostasis activate specific gene expression programs and are central to the acquisition and the plastic storage of memories. DREAM /KChIP proteins form heterotetramers that bind DNA and repress transcription in a Ca2+-dependent manner. Single ablation of one member of the DREAM/KChIP family may result in a mild or the absence of phenotype due to partial gene compensation. To study the function of DREAM/KChIP proteins in the brain, we used transgenic mice expressing a Ca2+-insensitive/CREB-independent dominant active mutant DREAM (daDREAM). We show that daDREAM controls the expression of several activity-dependent transcription factors including Npas4, Nr4a1, Mef2C, JunB and c-Fos, as well as the chromatin modifying enzyme Mbd4 and proteins related to actin polymerization like Arc and gelsolin. Thus, directly or through these targets, expression of daDREAM in the forebrain resulted in a complex phenotype characterized by i) impaired learning and memory, ii) loss of recurrent inhibition and enhanced LTP in the dentate gyrus without affecting Kv4-mediated potassium currents, and iii) modified spine density in DG granule neurons. Our results propose DREAM as a master-switch transcription factor regulating several activity-dependent gene expression programs to control synaptic plasticity, learning and memory.
DREAM controls the on/off switch of specific activity-dependent transcription pathways.
Specimen part
View SamplesMndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth and may modify plasmacytoma susceptibility.
Mndal, a new interferon-inducible family member, is highly polymorphic, suppresses cell growth, and may modify plasmacytoma susceptibility.
Specimen part, Time
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The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.
Specimen part
View SamplesThe cohesin offloading protein Wapal also acts as a polycomb factor in flies. We examined its role in transcriptional role in murine embryonic stem cells (ESCs)
The cohesin-associated protein Wapal is required for proper Polycomb-mediated gene silencing.
Specimen part
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