Different NR2 subunits (NR2A-D) of NMDA receptors confer distinct properties on the receptors and the subunit composition of heteromeric NMDA receptor complex is tightly regulated. Here, we demonstrate that suppression of neuronal activity causes mRNA expression of the NR2B subunit to increase significantly, both in vitro and in vivo, and that this modulation of transcription is mediated by epigenetic mechanisms. Treating cortical neurons with TTX substantially increases the level of mRNAs for NMDA receptor subunits. Particularly, the NR2B expression increases over 2-fold, similar to the effects of dark-rearing. The increase of NR2B induced by TTX is occluded by inhibiting DNMTs. Furthermore, MeCP2 binds to NR2B and the association of MeCP2 with NR2B is reduced by TTX treatment. Together, these data indicate that DNA methylation as well as subsequent MeCP2 association mediates neuronal activity-dependent regulation of NR2B expressions.
|Number of pages||5|
|Journal||Biochemical and biophysical research communications|
|Publication status||Published - 2008 Dec 19|
Bibliographical noteFunding Information:
This work was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-331-E00021) and a Korea University Grant. We thank Yoonjung Ko for technical assistance.
Copyright 2009 Elsevier B.V., All rights reserved.
- DNA methylation
- Epigenetic regulation
- NMDA receptor
- Synaptic plasticity
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology