title: Genome-wide analysis of chromatin regulation by cocaine reveals a role for sirtuins.
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.
authors.affiliation: Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: William
authors.initials: W
authors.lastname: Renthal
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar
authors.forename: Guanghua
authors.initials: G
authors.lastname: Xiao
authors.forename: Matthew
authors.initials: M
authors.lastname: Wilkinson
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Covington
authors.forename: Ian
authors.initials: I
authors.lastname: Maze
authors.forename: Devanjan
authors.initials: D
authors.lastname: Sikder
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Robison
authors.forename: Quincey
authors.initials: Q
authors.lastname: LaPlant
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.forename: Vincent
authors.initials: V
authors.lastname: Vialou
authors.forename: Sumana
authors.initials: S
authors.lastname: Chakravarty
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Kodadek
authors.forename: Ashley
authors.initials: A
authors.lastname: Stack
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kabbaj
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D002843:Chromatin / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D025461:Feedback, Physiological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D055106:Genome-Wide Association Study; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D012054:Reinforcement, Psychology; D015398:Signal Transduction / Q000187:drug effects; D037761:Sirtuins / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002843:Chromatin; D017362:Cyclic AMP Response Element-Binding Protein; D018765:Dopamine Uptake Inhibitors; C483819:Fosb protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D037761:Sirtuins; D003042:Cocaine