PMID- 15755907
OWN - NLM
STAT- MEDLINE
DCOM- 20050714
LR  - 20131121
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 67
IP  - 6
DP  - 2005 Jun
TI  - Neuron-restrictive silencer factor regulates the N-methyl-D-aspartate receptor 2B 
      subunit gene in basal and ethanol-induced gene expression in fetal cortical 
      neurons.
PG  - 2115-25
AB  - Neuron-restrictive silencer factor (NRSF) is a transcriptional repressor of 
      multiple neuronal genes. This study addressed the role of NRSF in 
      N-methyl-D-aspartate (NMDA) receptor NR2B promoter activity and the molecular 
      mechanisms of ethanol-induced NR2B up-regulation in fetal cortical neurons. The 
      5'-flanking region of the NR2B gene contains five NRSE-like elements. Functional 
      analysis of the upstream regions of the NR2B gene by transient transfection of 
      neurons revealed that neuron-restrictive silencer element (NRSE) motifs located 
      between base pair -1407 and -2741 represses transcription of the gene. Analysis 
      by electrophoretic mobility shift assay and reporter gene assay identified NRSE2 
      and 3 as responsible for repressing NR2B gene transcription. The identity of NRSF 
      as the functional binding factor is suggested by the specific binding of in vitro 
      synthesized NRSF or cell lysate to the labeled probes and the specific 
      antibody-induced supershift. Furthermore, whereas mutations of NRSE2 and 3 motifs 
      increased the promoter activity, overexpression of NRSF reduced it significantly. 
      The pattern of NRSF expression during development was investigated and 
      demonstrated that the highest expression is on embryonic day 14 with moderate 
      expression on postnatal day 0, reflecting a possible role of NRSF as a regulator 
      during development. Treatment of cultured cortical neurons with 100 mM ethanol 
      for 5 days caused a significant decrease in the NRSF mRNA and protein levels, 
      NRSF/NRSE binding activity, and an increase in the promoter activity. Therefore, 
      our studies suggest that NRSF is a negative regulator of NR2B expression and may 
      contribute to the ethanol-induced up-regulation of the NR2B gene in fetal 
      cortical neurons.
FAU - Qiang, Mei
AU  - Qiang M
AD  - Department of Pharmacology, University of Texas Health Science Center at San 
      Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. 
      qiang@uthscsa.edu
FAU - Rani, C S Sheela
AU  - Rani CS
FAU - Ticku, Maharaj K
AU  - Ticku MK
LA  - eng
GR  - R37 AA 12297-03/AA/NIAAA NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050308
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Ethanol/*pharmacology
MH  - Fetus
MH  - Gene Expression Regulation, Developmental/drug effects/physiology
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/*drug effects/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*biosynthesis/genetics
MH  - Repressor Proteins/*physiology
MH  - Transcription Factors/*physiology
EDAT- 2005/03/10 09:00
MHDA- 2005/07/15 09:00
CRDT- 2005/03/10 09:00
PHST- 2005/03/10 09:00 [pubmed]
PHST- 2005/07/15 09:00 [medline]
PHST- 2005/03/10 09:00 [entrez]
AID - mol.104.010751 [pii]
AID - 10.1124/mol.104.010751 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2005 Jun;67(6):2115-25. doi: 10.1124/mol.104.010751. Epub 2005 Mar 
      8.