PMID- 10792430
OWN - NLM
STAT- MEDLINE
DCOM- 20000724
LR  - 20190815
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 12
IP  - 5
DP  - 2000 May
TI  - Regulation of GluR2 promoter activity by neurotrophic factors via a 
      neuron-restrictive silencer element.
PG  - 1525-33
AB  - The AMPA glutamate receptor subunit GluR2, which plays a critical role in 
      regulation of AMPA channel function, shows altered levels of expression in vivo 
      after several chronic perturbations. To evaluate the possibility that 
      transcriptional mechanisms are involved, we studied a 1254-nucleotide fragment of 
      the 5'-promoter region of the mouse GluR2 gene in neural-derived cell lines. We 
      focused on regulation of GluR2 promoter activity by two neurotrophic factors, 
      which are known to be altered in vivo in some of the same systems that show GluR2 
      regulation. Glial-cell line derived neurotrophic factor (GDNF) and brain-derived 
      neurotrophic factor (BDNF) both induced GluR2 promoter activity. This was 
      associated with increased expression of endogenous GluR2 immunoreactivity in the 
      cells as measured by Western blotting. The effect of GDNF and BDNF appeared to be 
      mediated via a NRSE (neuron-restrictive silencer element) present within the 
      GluR2 promoter. The response to these neurotrophic factors was lost upon mutating 
      or deleting this site, but not several other putative response elements present 
      within the promoter. Moreover, overexpression of REST (restrictive element 
      silencer transcription factor; also referred to as NRSF or neuron restrictive 
      silencer factor), which is known to act on NRSEs in other genes to repress gene 
      expression, blocked the ability of GDNF to induce GluR2 promoter activity. 
      However, GDNF did not alter endogenous levels of REST in the cells. Together, 
      these findings suggest that GluR2 expression can be regulated by neurotrophic 
      factors via an apparently novel mechanism involving the NRSE present within the 
      GluR2 gene promoter.
FAU - Brene, S
AU  - Brene S
AD  - Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden. 
      stefan.brene@neuro.ki.se
FAU - Messer, C
AU  - Messer C
FAU - Okado, H
AU  - Okado H
FAU - Hartley, M
AU  - Hartley M
FAU - Heinemann, S F
AU  - Heinemann SF
FAU - Nestler, E J
AU  - Nestler EJ
LA  - eng
GR  - DA07359/DA/NIDA NIH HHS/United States
GR  - DA10140/DA/NIDA NIH HHS/United States
GR  - MH51399/MH/NIMH NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (GDNF protein, human)
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Recombinant Fusion Proteins)
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Gene Expression Regulation/*drug effects
MH  - *Gene Silencing
MH  - Genomic Library
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Humans
MH  - Mice
MH  - *Nerve Growth Factors
MH  - Nerve Tissue Proteins/*pharmacology
MH  - Neurons/*physiology
MH  - *Promoter Regions, Genetic/drug effects
MH  - Receptors, AMPA/*genetics
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Sequence Deletion
EDAT- 2000/05/03 09:00
MHDA- 2000/08/01 11:00
CRDT- 2000/05/03 09:00
PHST- 2000/05/03 09:00 [pubmed]
PHST- 2000/08/01 11:00 [medline]
PHST- 2000/05/03 09:00 [entrez]
AID - ejn040 [pii]
AID - 10.1046/j.1460-9568.2000.00040.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2000 May;12(5):1525-33. doi: 10.1046/j.1460-9568.2000.00040.x.