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

• DOI: 10.1126/science.1179438
• Publication Date: 2010-01-07T19:43:47Z
• Authors: Ian Maze; Herbert E. Covington; David M. Dietz; Quincey LaPlant; William Renthal; Scott J. Russo; Max Mechanic; Ezekiell Mouzon; Rachael L. Neve; Stephen J. Haggarty; Yanhua Ren; Srihari C. Sampath; Yasmin L. Hurd; Paul Greengard; Alexander Tarakho...; Anne Schaefer; Eric J. Nestler
• Keywords: Male; Neurons; 0301 basic medicine; Neuronal Plasticity; Behavior, Animal; Dendritic Spines; Gene Expression Profiling; Lysine; Down-Regulation; Histone-Lysine N-Methyltransferase; Methylation; Nucleus Accumbens; 3. Good health; Histones; Mice, Inbred C57BL; Cocaine-Related Disorders; Mice; 03 medical and health sciences; Cocaine; Gene Expression Regulation; Animals; Enzyme Repression; Oligonucleotide Array Sequence Analysis

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.