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

Academic Article
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Overview

authors

  • Renthal, W.
  • Kumar, A.
  • Xiao, G. H.
  • Wilkinson, M.
  • Covington, H. E.
  • Maze, I.
  • Sikder, D.
  • Robison, A. J.
  • LaPlant, Q.
  • Dietz, D. M.
  • Russo, S. J.
  • Vialou, V.
  • Chakravarty, S.
  • Kodadek, Thomas
  • Stack, A.
  • Kabbaj, M.
  • Nestler, E. J.

publication date

  • May 2009

journal

  • Neuron  Journal

abstract

  • 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.

subject areas

  • Animals
  • Chromatin
  • Cocaine
  • Cyclic AMP Response Element-Binding Protein
  • Dopamine Uptake Inhibitors
  • Feedback, Physiological
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nucleus Accumbens
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-fos
  • Reinforcement (Psychology)
  • Signal Transduction
  • Sirtuins
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Identity

PubMed Central ID

  • PMC2779727

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2009.03.026

PubMed ID

  • 19447090
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Additional Document Info

start page

  • 335

end page

  • 348

volume

  • 62

issue

  • 3

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