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Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
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Epigenetic programming of mu-opioid receptor gene in mouse brain is regulated by MeCP2 and Brg1 chromatin remodelling

Cheol Kyu Hwang1, Kyu Young Song, Chun Sung Kim

  • 1Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA.

Journal of Cellular and Molecular Medicine
|July 16, 2009
PubMed

Insights

The mu-opioid receptor (MOR) gene expression in the brain is epigenetically controlled. DNA methylation and histone modifications, influenced by methyl-CpG-binding protein 2 (MeCP2), regulate MOR expression in different brain regions.

Area of Science:

  • Neuroscience
  • Epigenetics
  • Pharmacology

Background:

  • The mu-opioid receptor (MOR) mediates morphine's pain-relieving effects and is spatially expressed in specific brain regions.
  • The precise mechanisms governing this unique spatial expression pattern of MOR have remained largely undetermined.
  • Previous research indicated DNA methylation regulates MOR in P19 cells.

Purpose of the Study:

  • To investigate the role of epigenetic mechanisms, including DNA methylation and histone modifications, in regulating differential MOR expression across mouse brain regions.
  • To explore the involvement of methyl-CpG-binding protein 2 (MeCP2) in the epigenetic control of MOR gene expression.

Main Methods:

  • Analysis of DNA methylation and histone modifications in microdissected mouse brain regions.
  • Treatment of MOR-negative cells with demethylating agents and histone deacetylase inhibitors to assess MOR gene inducibility.
  • In vivo assessment of MeCP2 interaction with the MOR promoter and its association with chromatin remodeling factors like Brg1 and Dnmt1.

Main Results:

  • Differential MOR expression in mouse brain regions correlated with specific DNA methylation and histone modification patterns.
  • MOR expression was inducible in MOR-negative cells using epigenetic modulators, indicating gene silencing.
  • Increased in vivo MeCP2 interaction was observed in the cerebellum, correlating with hypermethylated MOR promoter and lowest MOR expression.

Conclusions:

  • MOR gene expression is epigenetically programmed across various brain regions.
  • MeCP2 plays a role in the epigenetic regulation of MOR, involving DNA methylation and chromatin remodeling of the MOR promoter.

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