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Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus

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Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus. / Bayraktar, Gonca; Yuanxiang, PingAn; Confettura, Alessandro D; Gomes, Guilherme M; Raza, Syed A; Stork, Oliver; Tajima, Shoji; Suetake, Isao; Karpova, Anna; Yildirim, Ferah; Kreutz, Michael R.

In: NEUROPSYCHOPHARMACOL, Vol. 45, No. 12, 29.07.2020, p. 2120-2130.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Bayraktar, G, Yuanxiang, P, Confettura, AD, Gomes, GM, Raza, SA, Stork, O, Tajima, S, Suetake, I, Karpova, A, Yildirim, F & Kreutz, MR 2020, 'Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus', NEUROPSYCHOPHARMACOL, vol. 45, no. 12, pp. 2120-2130. https://doi.org/10.1038/s41386-020-0780-2

APA

Bayraktar, G., Yuanxiang, P., Confettura, A. D., Gomes, G. M., Raza, S. A., Stork, O., Tajima, S., Suetake, I., Karpova, A., Yildirim, F., & Kreutz, M. R. (2020). Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus. NEUROPSYCHOPHARMACOL, 45(12), 2120-2130. https://doi.org/10.1038/s41386-020-0780-2

Vancouver

Bayraktar G, Yuanxiang P, Confettura AD, Gomes GM, Raza SA, Stork O et al. Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus. NEUROPSYCHOPHARMACOL. 2020 Jul 29;45(12):2120-2130. https://doi.org/10.1038/s41386-020-0780-2

Bibtex

@article{dc71ceb122d6459db9ab539a5cd3d277,
title = "Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus",
abstract = "DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.",
author = "Gonca Bayraktar and PingAn Yuanxiang and Confettura, {Alessandro D} and Gomes, {Guilherme M} and Raza, {Syed A} and Oliver Stork and Shoji Tajima and Isao Suetake and Anna Karpova and Ferah Yildirim and Kreutz, {Michael R}",
year = "2020",
month = jul,
day = "29",
doi = "10.1038/s41386-020-0780-2",
language = "English",
volume = "45",
pages = "2120--2130",
journal = "NEUROPSYCHOPHARMACOL",
issn = "0893-133X",
publisher = "NATURE PUBLISHING GROUP",
number = "12",

}

RIS

TY - JOUR

T1 - Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus

AU - Bayraktar, Gonca

AU - Yuanxiang, PingAn

AU - Confettura, Alessandro D

AU - Gomes, Guilherme M

AU - Raza, Syed A

AU - Stork, Oliver

AU - Tajima, Shoji

AU - Suetake, Isao

AU - Karpova, Anna

AU - Yildirim, Ferah

AU - Kreutz, Michael R

PY - 2020/7/29

Y1 - 2020/7/29

N2 - DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.

AB - DNA methylation is a crucial epigenetic mark for activity-dependent gene expression in neurons. Very little is known about how synaptic signals impact promoter methylation in neuronal nuclei. In this study we show that protein levels of the principal de novo DNA-methyltransferase in neurons, DNMT3A1, are tightly controlled by activation of N-methyl-D-aspartate receptors (NMDAR) containing the GluN2A subunit. Interestingly, synaptic NMDARs drive degradation of the methyltransferase in a neddylation-dependent manner. Inhibition of neddylation, the conjugation of the small ubiquitin-like protein NEDD8 to lysine residues, interrupts degradation of DNMT3A1. This results in deficits in promoter methylation of activity-dependent genes, as well as synaptic plasticity and memory formation. In turn, the underlying molecular pathway is triggered by the induction of synaptic plasticity and in response to object location learning. Collectively, the data show that plasticity-relevant signals from GluN2A-containing NMDARs control activity-dependent DNA-methylation involved in memory formation.

U2 - 10.1038/s41386-020-0780-2

DO - 10.1038/s41386-020-0780-2

M3 - SCORING: Journal article

C2 - 32726795

VL - 45

SP - 2120

EP - 2130

JO - NEUROPSYCHOPHARMACOL

JF - NEUROPSYCHOPHARMACOL

SN - 0893-133X

IS - 12

ER -