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

Sangwoo Lee, Wonju Kim, Byung-Joo Ham, Wendy Chen, Mark F. Bear, Bongjune Yoon

Research output: Contribution to journalArticle

16 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 languageEnglish
Pages (from-to)930-934
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume377
Issue number3
DOIs
Publication statusPublished - 2008 Dec 19

Fingerprint

N-Methyl-D-Aspartate Receptors
Epigenomics
Messenger RNA
DNA Methylation
Association reactions
Transcription
Neurons
Modulation
Chemical analysis
In Vitro Techniques
NR2A NMDA receptor

Keywords

  • DNA methylation
  • Epigenetic regulation
  • MeCP2
  • NMDA receptor
  • NR2B
  • Synaptic plasticity

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

Cite this

Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation. / Lee, Sangwoo; Kim, Wonju; Ham, Byung-Joo; Chen, Wendy; Bear, Mark F.; Yoon, Bongjune.

In: Biochemical and Biophysical Research Communications, Vol. 377, No. 3, 19.12.2008, p. 930-934.

Research output: Contribution to journalArticle

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AU - Kim, Wonju

AU - Ham, Byung-Joo

AU - Chen, Wendy

AU - Bear, Mark F.

AU - Yoon, Bongjune

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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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