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

Molecular and Cellular Biology
Britt MellströmJose R Naranjo

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 indic...Continue Reading

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Citations

Jan 12, 2016·The Journal of Clinical Investigation·José R NaranjoBritt Mellström
Mar 2, 2016·Molecular Brain·Britt MellströmJavier DeFelipe
Nov 3, 2016·Pharmaceutical Patent Analyst·Hermann Am Mucke
Jan 10, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jaehyung Cho
Feb 21, 2016·Journal of Neurochemistry·Tomaso BenedetJose R Naranjo
Dec 23, 2015·International Journal of Molecular Sciences·Fong Chan ChoyMartin D Lewis
Dec 14, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·G MomtaziB C Schock
Dec 19, 2018·Frontiers in Molecular Neuroscience·Rocío NaranjoJosé R Naranjo
Feb 12, 2019·Frontiers in Molecular Neuroscience·Yu-Peng GuoYing Zhang
May 16, 2019·Scientific Reports·Alejandro Lopez-HurtadoMarta Gutierrez-Rodriguez
Jan 9, 2019·Frontiers in Molecular Neuroscience·Isabelle NéantCatherine Leclerc
Dec 19, 2020·Clinical Neurology and Neurosurgery·Cynthia A SmithAntonios Mammis
Nov 10, 2021·The Journal of Experimental Medicine·Jing LiJaehyung Cho

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Software Mentioned

QuantityOne
affy package
FIESTA viewer
limma
DREAM
Bioconductor
daDREAM

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