Essential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity

Author:

Maze Ian1,Covington Herbert E.1,Dietz David M.1,LaPlant Quincey12,Renthal William2,Russo Scott J.1,Mechanic Max2,Mouzon Ezekiell1,Neve Rachael L.3,Haggarty Stephen J.45,Ren Yanhua1,Sampath Srihari C.6,Hurd Yasmin L.1,Greengard Paul7,Tarakhovsky Alexander6,Schaefer Anne7,Nestler Eric J.1

Affiliation:

1. Fishberg Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA.

2. Departments of Psychiatry and Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX, USA.

3. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.

4. Psychiatric and Neurodevelopmental Genetics Unit and Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.

5. Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA, USA.

6. Laboratory of Lymphocyte Signaling, The Rockefeller University, New York, NY, USA.

7. Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.

Abstract

Cocaine Addiction and Histone Methylation Long-lasting behavioral syndromes associated with chronic cocaine exposure may result from dysregulation of the global transcriptional machinery. Maze et al. (p. 213 ) observed that histone lysine methylation in the nucleus accumbens plays a critical role in mediating the regulation of gene expression in response to repeated cocaine self-administration. Chronic cocaine was linked to overall reductions in dimethylation of lysine 9 of histone 3 (H3K9) in this brain region. Repressing H3K9 after chronic cocaine administration facilitated reward-related changes in behavior. The authors identifed the methyltransferase G9a as an essential mediator and an important regulator of dendritic spine plasticity. Downregulation of G9a was linked to the transcription factor ΔFosB.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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