Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation

Sangwoo Lee; Wonju Kim; Byung Joo Ham; Wendy Chen; Mark F. Bear; Bong June Yoon

doi:10.1016/j.bbrc.2008.10.082

Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation

Sangwoo Lee, Wonju Kim, Byung Joo Ham, Wendy Chen, Mark F. Bear, Bong June Yoon

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	930-934
Number of pages	5
Journal	Biochemical and biophysical research communications
Volume	377
Issue number	3
DOIs	https://doi.org/10.1016/j.bbrc.2008.10.082
Publication status	Published - 2008 Dec 19

Bibliographical note

Funding 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:
Copyright 2009 Elsevier B.V., All rights reserved.

Keywords

DNA methylation
Epigenetic regulation
MeCP2
NMDA receptor
NR2B
Synaptic plasticity

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2008.10.082

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title = "Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation",

abstract = "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.",

keywords = "DNA methylation, Epigenetic regulation, MeCP2, NMDA receptor, NR2B, Synaptic plasticity",

author = "Sangwoo Lee and Wonju Kim and Ham, {Byung Joo} and Wendy Chen and Bear, {Mark F.} and Yoon, {Bong June}",

note = "Funding 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: Copyright 2009 Elsevier B.V., All rights reserved.",

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AU - Bear, Mark F.

AU - Yoon, Bong June

N1 - Funding 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: Copyright 2009 Elsevier B.V., All rights reserved.

PY - 2008/12/19

Y1 - 2008/12/19

N2 - 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.

AB - 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.

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KW - Synaptic plasticity

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Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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