title: Tet1 Oxidase Regulates Neuronal Gene Transcription, Active DNA Hydroxy-methylation, Object Location Memory, and Threat Recognition Memory.
abstract: A dynamic equilibrium between DNA methylation and demethylation of neuronal activity-regulated genes is crucial for memory processes. However, the mechanisms underlying this equilibrium remain elusive. Tet1 oxidase has been shown to play a key role in the active DNA demethylation in the CNS. In this study, we usedTet1gene knockout (Tet1KO) mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found thatTet1ablation leads to: altered expression of numerous neuronal activity-regulated genes, compensatory upregulation of active demethylation pathway genes, and upregulation of various epigenetic modifiers. Moreover, Tet1KO mice showed an enhancement in the consolidation and storage of threat recognition (cued and contextual fear conditioning) and object location memories. We conclude that Tet1 plays a critical role in regulating neuronal transcription and in maintaining the epigenetic state of the brain associated with memory consolidation and storage.
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Milan
authors.initials: M
authors.lastname: Aggarwal
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Garrett A
authors.initials: GA
authors.lastname: Kaas
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: John
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology & Toxicology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Ross
authors.affiliation: Institute for Cell Engineering, Department of Neurology, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhong
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Kennedy
authors.affiliation: Institute for Cell Engineering, Department of Neurology, Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Sweatt
keywords: Cytosine methylation; DNA; HDAC; TET; active demethylation; chromatin; epigenetic; fear conditioning; gene expression; homeostatic plasticity; hydroxymethylcytosine; learning; memory; metaplasticity; motor learning; neuroepigenetics; threat conditioning; transcription; transcription factor