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

Sun, HaoSheng and Damez-Werno, Diane M and Scobie, Kimberly N and Shao, Ning-Yi and Dias, Caroline and Rabkin, Jacqui and Koo, Ja Wook and Korb, Erica and Bagot, Rosemary C and Ahn, Francisca H and Cahill, Michael E and Labonté, Benoit and Mouzon, Ezekiell and Heller, Elizabeth A and Cates, Hannah and Golden, Sam A and Gleason, Kelly and Russo, Scott J and Andrews, Simon and Neve, Rachael and Kennedy, Pamela J and Maze, Ian and Dietz, David M and Allis, C David and Turecki, Gustavo and Varga Weisz, Patrick and Tamminga, Carol and Shen, Li and Nestler, Eric J (2015) 'ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.' Nature Medicine, 21 (10). 1146 - 1153. ISSN 1078-8956

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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.

Item Type: Article
Uncontrolled Keywords: Animals, Mice, Inbred C57BL, Humans, Mice, Chromosomal Proteins, Non-Histone, Transcription Factors, Depression, Stress, Psychological, Chromatin Assembly and Disassembly, Male
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Elements
Date Deposited: 22 Apr 2021 12:07
Last Modified: 22 Apr 2021 13:15
URI: http://repository.essex.ac.uk/id/eprint/21419

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