TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation

GarrettA Kaas, Chun Zhong, DawnE Eason, DanielL Ross, RajV Vachhani, Guo li Ming, JenniferR King, Hongjun Song, J. David Sweatt

Research output: Contribution to journalArticle

Abstract

Dynamic changes in 5-methylcytosine (5mC) have been implicated in the regulation of gene expression critical for consolidation of memory. However, little is known about how these changes in 5mC are regulated in the adult brain. The enzyme methylcytosine dioxygenase TET1 (TET1) has been shown to promote active DNA demethylation in the nervous system. Therefore, we took a viral-mediated approach to overexpress the protein in the hippocampus and examine its potential involvement in memory formation. We found that Tet1 is a neuronal activity-regulated gene and that its overexpression leads to globalchanges in modified cytosine levels. Furthermore, expression of TET1 or a catalytically inactive mutant (TET1m) resulted in the upregulation of several neuronal memory-associated genes and impaired contextual fear memory. In summary, we show that neuronal Tet1 regulates DNA methylation levels and that its expression, independent of its catalytic activity, regulates the expression of CNS activity-dependent genes and memory formation.

Original languageEnglish (US)
Pages (from-to)1086-1093
Number of pages8
JournalNeuron
Volume79
Issue number6
DOIs
StatePublished - Sep 18 2013

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kaas, G., Zhong, C., Eason, D., Ross, D., Vachhani, R., Ming, G. L., King, J., Song, H., & Sweatt, J. D. (2013). TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation. Neuron, 79(6), 1086-1093. https://doi.org/10.1016/j.neuron.2013.08.032