Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.
|Title||Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Sun H, Damez-Werno DM, Scobie KN, Shao N-Y, Dias C, Rabkin J, Wright KN, Mouzon E, Kabbaj M, Neve R, Turecki G, Shen L, Nestler EJ|
|Date Published||2017 Jun 14|
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.
|PubMed Central ID||PMC5473651|
|Grant List||P01 DA008227 / DA / NIDA NIH HHS / United States |
R01 DA007359 / DA / NIDA NIH HHS / United States