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Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice

Abstract

DNA methylation regulates gene transcription and has been suggested to encode psychopathologies derived from early life stress. We found that methylation regulated the expression of the Crf (also known as Crh) gene and that chronic social stress in adult mice induced long-term demethylation of this genomic region. Demethylation was observed only in the subset of defeated mice that displayed social avoidance and site-specific knockdown of Crf attenuated the stress-induced social avoidance.

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Figure 1: Methylation of the Crf promoter regulates gene expression.
Figure 2: Stress-induced demethylation of Crf promoter coincides with social avoidance behavior.
Figure 3: Knockdown of Crf in PVN attenuates social avoidance after chronic social defeat.

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Acknowledgements

This work was supported by Roberto and Renata Ruhman, Mark Besen and the Pratt Foundation, the Israel Science Foundation, the Legacy Heritage Biomedical Science program of the Israel Science Foundation, the Nella and Leon Benoziyo Center for Neurosciences, the Nella and Leon Benoziyo Center for Neurological Diseases, the Carl and Micaela Einhorn-Dominic Brain Research Institute, the Irwin Green Alzheimer's Research Fund, and Gerhard and Hannah Bacharach. A.C. is incumbent of the Philip Harris and Gerald Ronson Career Development Chair.

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E.E. performed the cell culture experiments, in vivo DNA methylation and mRNA analysis, and behavioral experimentation. G.E.-N. performed stereotaxic surgery and viral injections. L.R. and A.N.-C. verified the Crf knockdown lentivirus. E.E. and A.C. designed the experiments, interpreted the results and wrote the manuscript.

Corresponding author

Correspondence to Alon Chen.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6, Supplementary Table 1 and Supplementary Methods (PDF 1104 kb)

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Elliott, E., Ezra-Nevo, G., Regev, L. et al. Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat Neurosci 13, 1351–1353 (2010). https://doi.org/10.1038/nn.2642

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