Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine

Hao Sheng Sun, Diane M. Damez-Werno, Kimberly N. Scobie, Ning Yi Shao, Caroline Dias, Jacqui Rabkin, Katherine N. Wright, Ezekiell Mouzon, Mohamed Kabbaj, Rachael Neve, Gustavo Turecki, Li Shen, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalNeuroscience
Volume353
DOIs
StatePublished - 14 Jun 2017

Keywords

  • addiction
  • chromatin
  • chromatin remodeling
  • cocaine
  • epigenetics

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