Document Detail

Activity-dependent NR2B expression is mediated by MeCP2-dependent epigenetic regulation.
MedLine Citation:
PMID:  18952054     Owner:  NLM     Status:  MEDLINE    
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.
Sangwoo Lee; Wonju Kim; Byung-Joo Ham; Wendy Chen; Mark F Bear; Bong-June Yoon
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-10-24
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  377     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-25     Completed Date:  2008-12-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  930-4     Citation Subset:  IM    
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
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MeSH Terms
DNA Methylation
Epigenesis, Genetic*
Methyl-CpG-Binding Protein 2 / metabolism*
Neurons / metabolism,  physiology
Rats, Inbred LEC
Receptors, N-Methyl-D-Aspartate / genetics*
Visual Cortex / cytology,  metabolism,  physiology*
Reg. No./Substance:
0/Mecp2 protein, rat; 0/Methyl-CpG-Binding Protein 2; 0/NR2B NMDA receptor; 0/Receptors, N-Methyl-D-Aspartate

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