PMID- 18201839
OWN - NLM
STAT- MEDLINE
DCOM- 20080612
LR  - 20211020
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 151
IP  - 4
DP  - 2008 Feb 19
TI  - Epigenetic regulation of kappa opioid receptor gene in neuronal differentiation.
PG  - 1034-41
LID - 10.1016/j.neuroscience.2007.12.015 [doi]
AB  - The gene of mouse kappa opioid receptor (KOR) utilizes two promoters, P1 and P2. 
      P1 is active in various brain areas and constitutively in P19 mouse embryonal 
      carcinoma cells. P2 is active in limited brain stem areas of adult animals and 
      only in late differentiated cells of P19 induced for neuronal differentiation in 
      the presence of nerve growth factor (NGF). NGF response of P2 was found to be 
      mediated by a specific binding site for transcription factor activation protein 2 
      (AP2) located in P2. Electrophoretic gel shift assay showed specific binding of 
      this AP2 site by AP2beta, but not AP2alpha. Knockdown of endogenous AP2beta with 
      siRNA abolished the stimulating effect of NGF on the expression of transcripts 
      driven by P2. Binding of endogenous AP2beta on the endogenous KOR P2 chromatin 
      region was also confirmed by chromatin immunoprecipitation. The effect of NGF was 
      inhibited by LY2942002 (phosphatidylinositol 3-kinase, PI3K inhibitor), 
      suggesting that PI3K was involved in signaling pathway mediating the effect of 
      NGF stimulation on KOR P2. The chromatin of P2 in P19 was found to be 
      specifically modified following NGF stimulation, which included demethylation at 
      Lys9 and dimethylation at Lys4 of histone H3 and was consistent with the 
      increased recruitment of RNA polymerase II to this promoter. This study presents 
      the first evidence for epigenetic changes occurred on a specific KOR promoter 
      triggered by NGF in cells undergoing neuronal differentiation. This epigenetic 
      change is mediated by recruited AP2beta to this promoter and involves the PI3K 
      system.
FAU - Park, S W
AU  - Park SW
AD  - Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson 
      Hall, 321 Church Street Southeast, Minneapolis, MN 55455, USA.
FAU - He, Y
AU  - He Y
FAU - Ha, S G
AU  - Ha SG
FAU - Loh, H H
AU  - Loh HH
FAU - Wei, L-N
AU  - Wei LN
LA  - eng
GR  - K02 DA013926-05/DA/NIDA NIH HHS/United States
GR  - R01 DA011190-11A1/DA/NIDA NIH HHS/United States
GR  - R01 DK060521/DK/NIDDK NIH HHS/United States
GR  - R01 DA000564/DA/NIDA NIH HHS/United States
GR  - P50 DA011806/DA/NIDA NIH HHS/United States
GR  - R56 DA000564/DA/NIDA NIH HHS/United States
GR  - K02 DA013926-06/DA/NIDA NIH HHS/United States
GR  - DA11190/DA/NIDA NIH HHS/United States
GR  - DK54733/DK/NIDDK NIH HHS/United States
GR  - K02 DA013926/DA/NIDA NIH HHS/United States
GR  - P50 DA011806-100001/DA/NIDA NIH HHS/United States
GR  - K02-DA13926/DA/NIDA NIH HHS/United States
GR  - DA001583/DA/NIDA NIH HHS/United States
GR  - DA011806/DA/NIDA NIH HHS/United States
GR  - DA000564/DA/NIDA NIH HHS/United States
GR  - R01 DA011190-10/DA/NIDA NIH HHS/United States
GR  - R01 DK054733-07/DK/NIDDK NIH HHS/United States
GR  - R01 DA001583/DA/NIDA NIH HHS/United States
GR  - DK60521/DK/NIDDK NIH HHS/United States
GR  - R01 DA011190/DA/NIDA NIH HHS/United States
GR  - K05-DA070554/DA/NIDA NIH HHS/United States
GR  - R01 DK060521-05/DK/NIDDK NIH HHS/United States
GR  - R01 DK054733/DK/NIDDK NIH HHS/United States
GR  - K05 DA070554/DA/NIDA NIH HHS/United States
GR  - DA11806/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080116
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 5688UTC01R (Tretinoin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/drug effects/*physiology
MH  - Chromatin Immunoprecipitation/methods
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Electrophoretic Mobility Shift Assay/methods
MH  - Enzyme Inhibitors/pharmacology
MH  - Epigenesis, Genetic/drug effects/*physiology
MH  - Luciferases/metabolism
MH  - Mice
MH  - Models, Biological
MH  - Nerve Growth Factor/pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - PC12 Cells/drug effects
MH  - Promoter Regions, Genetic/drug effects
MH  - RNA, Small Interfering/metabolism/pharmacology
MH  - Rats
MH  - Receptors, Opioid, kappa/*genetics/metabolism
MH  - Transfection
MH  - Tretinoin/pharmacology
PMC - PMC2265776
MID - NIHMS40937
EDAT- 2008/01/19 09:00
MHDA- 2008/06/13 09:00
PMCR- 2009/02/19
CRDT- 2008/01/19 09:00
PHST- 2007/10/01 00:00 [received]
PHST- 2007/12/03 00:00 [revised]
PHST- 2007/12/07 00:00 [accepted]
PHST- 2008/01/19 09:00 [pubmed]
PHST- 2008/06/13 09:00 [medline]
PHST- 2008/01/19 09:00 [entrez]
PHST- 2009/02/19 00:00 [pmc-release]
AID - S0306-4522(07)01560-6 [pii]
AID - 10.1016/j.neuroscience.2007.12.015 [doi]
PST - ppublish
SO  - Neuroscience. 2008 Feb 19;151(4):1034-41. doi: 
      10.1016/j.neuroscience.2007.12.015. Epub 2008 Jan 16.