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

Fingerprint

5-Methylcytosine
Hydroxylation
DNA
Genes
Dioxygenases
Cytosine
Gene Expression Regulation
DNA Methylation
Nervous System
Fear
Hippocampus
Up-Regulation
Brain
Enzymes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kaas, G., Zhong, C., Eason, D., Ross, D., Vachhani, R., Ming, G. L., ... 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

TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation. / Kaas, GarrettA; Zhong, Chun; Eason, DawnE; Ross, DanielL; Vachhani, RajV; Ming, Guo li; King, JenniferR; Song, Hongjun; Sweatt, J. David.

In: Neuron, Vol. 79, No. 6, 18.09.2013, p. 1086-1093.

Research output: Contribution to journalArticle

Kaas, G, Zhong, C, Eason, D, Ross, D, Vachhani, R, Ming, GL, King, J, Song, H & Sweatt, JD 2013, 'TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation', Neuron, vol. 79, no. 6, pp. 1086-1093. https://doi.org/10.1016/j.neuron.2013.08.032
Kaas, GarrettA ; Zhong, Chun ; Eason, DawnE ; Ross, DanielL ; Vachhani, RajV ; Ming, Guo li ; King, JenniferR ; Song, Hongjun ; Sweatt, J. David. / TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation. In: Neuron. 2013 ; Vol. 79, No. 6. pp. 1086-1093.
@article{adb86b37984446a9a8ce52d6a5746591,
title = "TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation",
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.",
author = "GarrettA Kaas and Chun Zhong and DawnE Eason and DanielL Ross and RajV Vachhani and Ming, {Guo li} and JenniferR King and Hongjun Song and Sweatt, {J. David}",
year = "2013",
month = "9",
day = "18",
doi = "10.1016/j.neuron.2013.08.032",
language = "English (US)",
volume = "79",
pages = "1086--1093",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - TET1 controls CNS 5-Methylcytosine Hydroxylation, active DNA demethylation, gene transcription, and memory formation

AU - Kaas, GarrettA

AU - Zhong, Chun

AU - Eason, DawnE

AU - Ross, DanielL

AU - Vachhani, RajV

AU - Ming, Guo li

AU - King, JenniferR

AU - Song, Hongjun

AU - Sweatt, J. David

PY - 2013/9/18

Y1 - 2013/9/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84884471932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884471932&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2013.08.032

DO - 10.1016/j.neuron.2013.08.032

M3 - Article

C2 - 24050399

AN - SCOPUS:84884471932

VL - 79

SP - 1086

EP - 1093

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -