PMID- 15322094
OWN - NLM
STAT- MEDLINE
DCOM- 20041228
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 45
DP  - 2004 Nov 5
TI  - Neuron-restrictive silencer factor (NRSF) functions as a repressor in neuronal 
      cells to regulate the mu opioid receptor gene.
PG  - 46464-73
AB  - The mu opioid receptor (MOR) is expressed in the central nervous system and 
      specific cell lines with varying expression levels perhaps playing important 
      roles. One of the neuronal-specific transcription regulators, neuron-restrictive 
      silencer factor (NRSF), has been shown to repress the expression of 
      neuron-specific genes in non-neuronal cells. However, we showed here that the 
      neuron-restrictive silencer element (NRSE) of MOR functions as a critical 
      regulator to repress the MOR gene expression in specific neuronal cells depending 
      on NRSF expression level. Using co-transfection studies, we showed that the NRSE 
      of the MOR promoter is functional in NRSF-positive cells (NS20Y and HeLa) but not 
      in NRSF-negative cells (PC12). NRSF binds to the NRSE of the MOR gene in a 
      sequence-specific manner confirmed by supershift and chromatin 
      immunoprecipitation assays, respectively. The suppression of NRSF activity with 
      either trichostatin A or a dominant-negative NRSF induced MOR promoter activity 
      and transcription of the MOR gene. When the NRSF was disrupted in NS20Y and HeLa 
      cells using small interfering RNA, the transcription of the endogenous target MOR 
      gene increased significantly. This provides direct evidence the role of NRSF in 
      the cells and also indicates that NRSF expression is regulated by 
      post-translational modification in neuronal NMB cells. Our data suggested that 
      NRSF can function as a repressor of MOR transcription in specific cells, via a 
      mechanism dependent on the MOR NRSE.
FAU - Kim, Chun Sung
AU  - Kim CS
AD  - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, 
      Minnesota 55455, USA. kimxx313@umn.edu
FAU - Hwang, Cheol Kyu
AU  - Hwang CK
FAU - Choi, Hack Sun
AU  - Choi HS
FAU - Song, Kyu Young
AU  - Song KY
FAU - Law, Ping-Yee
AU  - Law PY
FAU - Wei, Li-Na
AU  - Wei LN
FAU - Loh, Horace H
AU  - Loh HH
LA  - eng
GR  - DA00564/DA/NIDA NIH HHS/United States
GR  - DA01583/DA/NIDA NIH HHS/United States
GR  - DA11190/DA/NIDA NIH HHS/United States
GR  - DA11806/DA/NIDA NIH HHS/United States
GR  - DA13926/DA/NIDA NIH HHS/United States
GR  - K05-DA70554/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040818
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chromatin)
RN  - 0 (RE1-silencing transcription factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factors)
RN  - 63231-63-0 (RNA)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Cell Nucleus/metabolism
MH  - Chromatin/metabolism
MH  - *Gene Expression Regulation
MH  - Genes, Dominant
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Immunoprecipitation
MH  - Luciferases/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neurons/*metabolism
MH  - PC12 Cells
MH  - Plasmids/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Processing, Post-Translational
MH  - RNA/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Rats
MH  - Receptors, Opioid, mu/*genetics
MH  - Repressor Proteins/metabolism/*physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Time Factors
MH  - Transcription Factors/metabolism/*physiology
MH  - Transcription, Genetic
MH  - Transfection
EDAT- 2004/08/24 05:00
MHDA- 2004/12/29 09:00
CRDT- 2004/08/24 05:00
PHST- 2004/08/24 05:00 [pubmed]
PHST- 2004/12/29 09:00 [medline]
PHST- 2004/08/24 05:00 [entrez]
AID - S0021-9258(20)69853-2 [pii]
AID - 10.1074/jbc.M403633200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Nov 5;279(45):46464-73. doi: 10.1074/jbc.M403633200. Epub 2004 
      Aug 18.