Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors

@article{Heller2014LocusspecificER,
  title={Locus-specific epigenetic remodeling controls addiction- and depression-related behaviors},
  author={Elizabeth A. Heller and Hannah M. Cates and Catherine Jensen Pe{\~n}a and HaoSheng Sun and Ning-Yi Shao and Jian Feng and Sam A. Golden and James P. Herman and Jessica J. Walsh and Michelle S Mazei-Robison and Deveroux Ferguson and Scott W. Knight and Mark A. Gerber and Christian J Nievera and Ming-Hu Han and Scott J. Russo and Carol Tamminga and Rachael L. Neve and Li Shen and H. Steve Zhang and Feng Zhang and Eric J. Nestler},
  journal={Nature Neuroscience},
  year={2014},
  volume={17},
  pages={1720-1727}
}
Chronic exposure to drugs of abuse or stress regulates transcription factors, chromatin-modifying enzymes and histone post-translational modifications in discrete brain regions. Given the promiscuity of the enzymes involved, it has not yet been possible to obtain direct causal evidence to implicate the regulation of transcription and consequent behavioral plasticity by chromatin remodeling that occurs at a single gene. We investigated the mechanism linking chromatin dynamics to neurobiological… 
Targeted Epigenetic Remodeling of the Cdk5 Gene in Nucleus Accumbens Regulates Cocaine- and Stress-Evoked Behavior
TLDR
A novel technology, zinc-finger engineered transcription factors, are found to be sufficient to regulate the expression of Cdk5 and results in altered behavioral responses to cocaine and social stress, providing compelling evidence of the significance of epigenetic regulation in the neurobiological basis of reward- and stress-related neuropsychiatric disease.
It is a complex issue: emerging connections between epigenetic regulators in drug addiction
TLDR
This review focuses on the proteins and complexes contributing to epigenetic modifications in the nucleus accumbens (NAc) following drug experience and how targeting these multiprotein epigenetic enzyme complexes – and the individual proteins that comprise them – might lead to effective therapeutics to reverse or treat SUDs in patients.
Drug Addiction and Histone Code Alterations.
TLDR
This work has demonstrated that specific histone modifications are involved in addiction-related gene regulatory mechanisms, by a diverse set of histone-modifying enzymes and readers, which may prove to be valuable pharmacological targets for effective treatments for drug addiction.
Epigenetics and Drug Abuse
TLDR
This chapter highlights recent research demonstrating epigenetic changes in response to drug exposure with a focus on three different mechanisms: DNA methylation, histone modification, and noncod‐ ing RNAs.
Key transcription factors mediating cocaine-induced plasticity in the nucleus accumbens
TLDR
The literature on transcription factors mediating cocaine action in the NAc is synthesized, the advancements and remaining limitations of current experimental approaches are discussed, and recent work leveraging bioinformatic tools and neuroepigenomic editing to study transcription factors involved in cocaine addiction is emphasized.
Sex-Specific Regulation of Fear Memory by Targeted Epigenetic Editing of Cdk5
Epigenetic Mechanisms of Psychostimulant-Induced Addiction.
Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons
TLDR
Surprisingly, a small set of activity-regulated genes (ARG) encoding transcription factors, and a specific pattern of epigenetic marks on gene promoters, are conserved in dopaminergic neurons over the long evolutionary period between mammals and insects.
...
...

References

SHOWING 1-10 OF 55 REFERENCES
Transcriptional and epigenetic mechanisms of addiction
TLDR
Multiple mechanisms by which drugs alter the transcriptional potential of genes are reviewed, including alterations in the accessibility of genes within their native chromatin structure induced by histone tail modifications and DNA methylation, and the regulation of gene expression by non-coding RNAs.
Genome-wide Analysis of Chromatin Regulation by Cocaine Reveals a Role for Sirtuins
CBP in the Nucleus Accumbens Regulates Cocaine-Induced Histone Acetylation and Is Critical for Cocaine-Associated Behaviors
TLDR
The first study to demonstrate a definitive role for CBP in modulating gene expression that may subserve drug-seeking behaviors is demonstrated and correlates with significant impairments in cocaine sensitivity and context–cocaine associated memory.
Class I HDAC Inhibition Blocks Cocaine-Induced Plasticity Through Targeted Changes in Histone Methylation
TLDR
It is demonstrated that specific and prolonged blockade of HDAC1 in NAc of mice increased global levels of histone acetylation, but also induced repressive histone methylation and antagonized cocaine-induced changes in behavior.
Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity
TLDR
Using conditional mutagenesis and viral-mediated gene transfer, it is found that G9a down-regulation increased the dendritic spine plasticity of nucleus accumbens neurons and enhanced the preference for cocaine, thereby establishing a crucial role for histone methylation in the long-term actions of cocaine.
Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression
TLDR
The data identify epigenetic regulation of RAC1 in the NAc as a disease mechanism in depression and reveal a functional role for Rac1 in rodents in regulating stress-related behaviors.
Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens
TLDR
This delineation of the cocaine-induced epigenome in the nucleus accumbens reveals several novel modes of regulation by which cocaine alters the brain, and serves as a template for the analysis of other systems to reveal new transcriptional and epigenetic mechanisms of neuronal regulation.
Morphine Epigenomically Regulates Behavior through Alterations in Histone H3 Lysine 9 Dimethylation in the Nucleus Accumbens
TLDR
It is shown that chronic morphine, like cocaine, decreases G9a expression, and global levels of H3K9me2, in mouse nucleus accumbens (NAc), a key brain reward region, and that overexpression of G 9a in NAc opposes morphine reward and locomotor sensitization and concomitantly promotes analgesic tolerance and naloxone-precipitated withdrawal.
...
...