Tet1 oxidase regulates neuronal gene transcription, active DNA hydroxymethylation, object location memory, and threat recognition memory

Dinesh Kumar, Milan Aggarwal, Garrett A. Kaas, John Lewis, Jing Wang, Daniel L. Ross, Chun Zhong, Andrew Kennedy, Hongjun Song, J. David Sweatt

Research output: Contribution to journalArticlepeer-review

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 central nervous system. In this study, we used Tet1 gene knockout (Tet1KO) mice to examine the involvement of Tet1 in memory consolidation and storage in the adult brain. We found that Tet1 ablation 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.

Original languageEnglish (US)
Pages (from-to)12-27
Number of pages16
JournalNeuroepigenetics
Volume4
DOIs
StatePublished - Oct 1 2015

Keywords

  • Active demethylation
  • Cytosine methylation
  • Epigenetic
  • Fear conditioning
  • HDAC
  • Homeostatic plasticity
  • Hydroxymethylcytosine
  • Learning
  • Memory
  • Neuroepigenetics
  • TET
  • Threat conditioning

ASJC Scopus subject areas

  • Biochemistry
  • Biological Psychiatry
  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience
  • Developmental Neuroscience

Fingerprint Dive into the research topics of 'Tet1 oxidase regulates neuronal gene transcription, active DNA hydroxymethylation, object location memory, and threat recognition memory'. Together they form a unique fingerprint.

Cite this