Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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


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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. de Kloet, E.R., Joels, M. & Holsboer, F. Nat. Rev. Neurosci. 6, 463–475 (2005).

    CAS  Article  Google Scholar 

  2. McEwen, B.S. Physiol. Rev. 87, 873–904 (2007).

    Article  Google Scholar 

  3. Vale, W., Spiess, J., Rivier, C. & Rivier, J. Science 213, 1394–1397 (1981).

    CAS  Article  Google Scholar 

  4. Bale, T.L. & Vale, W.W. Annu. Rev. Pharmacol. Toxicol. 44, 525–557 (2004).

    CAS  Article  Google Scholar 

  5. Joels, M. & Baram, T.Z. Nat. Rev. Neurosci. 10, 459–466 (2009).

    CAS  Article  Google Scholar 

  6. McGowan, P.O. et al. Nat. Neurosci. 12, 342–348 (2009).

    CAS  Article  Google Scholar 

  7. Murgatroyd, C. et al. Nat. Neurosci. 12, 1559–1566 (2009).

    CAS  Article  Google Scholar 

  8. Roth, T.L., Lubin, F.D., Funk, A.J. & Sweatt, J.D. Biol. Psychiatry 65, 760–769 (2009).

    CAS  Article  Google Scholar 

  9. Mueller, B.R. & Bale, T.L. J. Neurosci. 28, 9055–9065 (2008).

    CAS  Article  Google Scholar 

  10. Zhang, X. et al. Proc. Natl. Acad. Sci. USA 102, 4459–4464 (2005).

    CAS  Article  Google Scholar 

  11. Aguilera, G., Kiss, A., Liu, Y. & Kamitakahara, A. Stress 10, 153–161 (2007).

    CAS  Article  Google Scholar 

  12. Krishnan, V. et al. Cell 131, 391–404 (2007).

    CAS  Article  Google Scholar 

  13. Ma, D.K. et al. Science 323, 1074–1077 (2009).

    CAS  Article  Google Scholar 

  14. Tsankova, N.M. et al. Nat. Neurosci. 9, 519–525 (2006).

    CAS  Article  Google Scholar 

  15. Paxinos, F. & Franklin, K.B.J. The Mouse Brain in Stereotaxic Coordinates (Academic Press, San Diego, California, 2001).

Download references


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.

Author information

Authors and Affiliations



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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing