[PDF][PDF] Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins

W Renthal, A Kumar, G Xiao, M Wilkinson… - Neuron, 2009 - cell.com
W Renthal, A Kumar, G Xiao, M Wilkinson, HE Covington, I Maze, D Sikder, AJ Robison…
Neuron, 2009cell.com
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 …
Summary
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 ΔFosB 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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