Journal Article

DZNE-2020-01316

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Synaptic control of DNA methylation involves activity-dependent degradation of DNMT3A1 in the nucleus

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. (Last author)DZNE*

2020
Nature Publishing Group11167 Basingstoke

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41386-020-0780-2

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.

Keyword(s): DNA Methylation (MeSH) ; Memory (MeSH) ; Neuronal Plasticity (MeSH) ; Neurons: metabolism (MeSH) ; Receptors, N-Methyl-D-Aspartate: genetics (MeSH) ; Receptors, N-Methyl-D-Aspartate: metabolism (MeSH) ; Synapses: metabolism (MeSH)

---

Contributing Institute(s):

1. Nuclear Function in CNS Pathophysiology (AG Salomoni)
2. U Preclinical Researchers T2 - Magdeburg (U Preclinical Researchers T2 - Magdeburg)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

---

Database coverage:
; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection

---