Essential role of the histone methyltransferase G91 in cocaine-induced plasticity (Science, 2010, 327:213-216)

報告日期: 2010/06/04
報告時間: 15:10/16:00
報告學生: 余泱蓉
講評老師: 游一龍

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


Ian Maze, Herbert E. Covington III, 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 Tarakhovsky, Anne Schaefer, Eric J. Nest

SCIENCE  327: 213-216, 2010


Speaker: Yu Yang-Jung (余泱蓉)

Commentator: Yu Lung (游一龍) Ph.D.

Date: 15:10-16:00, June 4, 2010

Place: Room 602



  Repeated addictive drug exposure such as cocaine exhibit potent rewarding properties and drug dependent. Previous studies investigated that persistent alternated gene expression and increased dendritic spine formation in neucleus accumbens (NAc) make cocaine-induced long-lasting change. In addition, chromatin remodeling acts as the major mechanism underlying cocaine-induce plasticity. Recent studies have suggested that cocaine regulates chromatin remodeling through histone acetylation and phosphorylation. However, role for histone methyaltion in cocaine-induced plasticity remains unknown. In this study, the authors found that both methyltransferase G9a catalyzing histone 3 lysine 9 (H3K9) methylation and the dimethylation of H3K9 (H3K9me2) level decreased after repeated cocaine exposure. Moreover, the overexpression of G9a reduced chronic cocaine-enhanced gene expression. According to previous studies, transcriptional factor DFosB was induced after chronic addictive drug exposure. Therefore, they used transgenic mice for overexpression or inhibition of DFosB without repeated cocaine exposure to decrease or increase the level of G9a and H3K9me2 respectively, similar to that observed after repeated cocaine exposure. In aspect of behavior response and dendritic spine morphology, overexpression or deletion of G9a could decrease or increase cocaine preference and dendritic spine formation respectively. Moreover, inhibition of DFosB activity decreased dendritic spine formation. Summarizing the result of the above, the authors demonstrate that both H3K9 and its enzyme G9a in the NAc play important roles in regulating neuronal gene expression and dendritic spine formation after chronic cocaine exposure. The finding could elaborate the complicated biological basis underlying drug addiction mechanism.



Genome-wide Analysis of Chromatin Regulation by Cocaine Reveals a Role for Sirtuins Neuron 62: 335–348, 2009