ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior

Haosheng Sun, Diane M. Damez-Werno, Kimberly N. Scobie, Ning Yi Shao, Caroline Dias, Jacqui Rabkin, Ja Wook Koo, Erica Korb, Rosemary C. Bagot, Francisca H. Ahn, Michael E. Cahill, Benoit Labonté, Ezekiell Mouzon, Elizabeth A. Heller, Hannah Cates, Sam A. Golden, Kelly Gleason, Scott J. Russo, Simon Andrews, Rachael NevePamela J. Kennedy, Ian Maze, David M. Dietz, C. David Allis, Gustavo Turecki, Patrick Varga-Weisz, Carol Tamminga, Li Shen, Eric J. Nestler

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.

Original languageEnglish (US)
Pages (from-to)1146-1153
Number of pages8
JournalNature Medicine
Volume21
Issue number10
DOIs
Publication statusPublished - Oct 1 2015

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sun, H., Damez-Werno, D. M., Scobie, K. N., Shao, N. Y., Dias, C., Rabkin, J., ... Nestler, E. J. (2015). ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior. Nature Medicine, 21(10), 1146-1153. https://doi.org/10.1038/nm.3939