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ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior
HaoSheng Sun1,2, Diane M Damez-Werno1,2, Kimberly N Scobie1,2
1Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Nature Medicine
|September 22, 2015
Summary
The ACF chromatin-remodeling complex is upregulated in stress-susceptible individuals and is essential for stress-induced depression. This complex alters gene expression by changing nucleosome positioning, impacting stress-related behaviors.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Major depressive disorder (MDD) treatment is limited by poor understanding of its biological basis.
- Stress-induced maladaptive transcriptional regulation in limbic circuits may drive MDD development.
- Epigenetic factors regulating chromatin structure are potential contributors.
Purpose of the Study:
- To investigate the role of the ACF complex in stress-induced depressive-like behaviors.
- To determine if ACF upregulation in the nucleus accumbens is linked to depression susceptibility.
- To explore the impact of ACF on gene expression and chromatin structure.
Main Methods:
- Utilized stress-susceptible mouse models and depressed human subjects.
- Assessed ACF complex expression and binding in the nucleus accumbens.
- Analyzed nucleosome positioning and gene expression changes after chronic stress.
Main Results:
- Persistent upregulation of the ACF complex was observed in stress-susceptible mice and depressed humans.
- Altered ACF binding correlated with changes in nucleosome positioning around transcription start sites.
- These epigenetic alterations were associated with repressed expression of stress-susceptibility genes.
Conclusions:
- The ACF (ATP-utilizing chromatin assembly and remodeling factor) complex is crucial for stress-induced depressive behaviors.
- ACF plays a key role in regulating stress-related behaviors through epigenetic modifications.
- Targeting the ACF complex may offer novel therapeutic strategies for MDD.
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