Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins.
paper
Cited
Public
- Authors
- Renthal, William; Kumar, Arvind; Xiao, Guanghua; Wilkinson, Matthew; Covington, Herbert E; Maze, Ian; Sikder, Devanjan; Robison, Alfred J; LaPlant, Quincey; Dietz, David M; Russo, Scott J; Vialou, Vincent; Chakravarty, Sumana; Kodadek, Thomas J; Stack, Ashley; Kabbaj, Mohamed; Nestler, Eric J
- Year
- 2009
- Journal
- Neuron
- PMID
- 19447090
- DOI
- 10.1016/j.neuron.2009.03.026
- PMCID
- PMC2779727
Changes in gene expression contribute to the long-lasting regulation of the brain's reward circuitry seen in drug addiction; however, the specific genes regulated and the transcriptional mechanisms underlying such regulation remain poorly understood. Here, we used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide chromatin changes in the mouse nucleus accumbens, a crucial brain reward region, after repeated cocaine administration. Our findings reveal several interesting principles of gene regulation by cocaine and of the role of DeltaFosB and CREB, two prominent cocaine-induced transcription factors, in this brain region. The findings also provide comprehensive insight into the molecular pathways regulated by cocaine-including a new role for sirtuins (Sirt1 and Sirt2)-which are induced in the nucleus accumbens by cocaine and, in turn, dramatically enhance the behavioral effects of the drug.
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