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

Neuroscience. 2017 Jun 14;353:1-6. doi: 10.1016/j.neuroscience.2017.04.007. Epub 2017 Apr 12.

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.

Keywords: addiction; chromatin; chromatin remodeling; cocaine; epigenetics.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chromatin Assembly and Disassembly / drug effects*
  • Chromosomal Proteins, Non-Histone / genetics*
  • Cocaine / administration & dosage*
  • Cocaine-Related Disorders / genetics
  • Conditioning, Classical / drug effects
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Nucleosomes / drug effects
  • Nucleosomes / metabolism
  • Nucleus Accumbens / metabolism*
  • RNA, Messenger / metabolism
  • Transcription Factors / genetics*

Substances

  • BAZ1A protein, human
  • BAZ1A protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Nucleosomes
  • RNA, Messenger
  • Transcription Factors
  • Cocaine