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Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation

Nature Chemical Biology volume 6, pages 267–269 (2010)Cite this article

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Abstract

We have developed a readily accessible disulfide-directed methodology for the site-specific modification of histones by ubiquitin and ubiquitin-like proteins. The disulfide-linked analog of mono-ubiquitylated H2B stimulated the H3K79 methyltransferase activity of hDot1L to a similar extent as the native isopeptide linkage. This permitted structure-activity studies of ubiquitylated mononucleosomes that revealed plasticity in the mechanism of hDot1L stimulation and identified surfaces of ubiquitin important for activation.

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Figure 1: Structure-activity relationships of ubiquitylated mononuclesomes.

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References

  1. Hershko, A. & Ciechanover, A. Annu. Rev. Biochem. 67, 425–479 (1998).

    Article  CAS  Google Scholar 

  2. Deshaies, R.J. & Joazeiro, C.A.P. Annu. Rev. Biochem. 78, 399–434 (2009).

    Article  CAS  Google Scholar 

  3. Goldknopf, I.L. & Busch, H. Proc. Natl. Acad. Sci. USA 74, 864–868 (1977).

    Article  CAS  Google Scholar 

  4. West, M.H. & Bonner, W.M. Nucleic Acids Res. 8, 4671–4680 (1980).

    Article  CAS  Google Scholar 

  5. Nickel, B.E., Allis, C.D. & Davie, J.R. Biochemistry 28, 958–963 (1989).

    Article  CAS  Google Scholar 

  6. Shilatifard, A. Annu. Rev. Biochem. 75, 243–269 (2006).

    Article  CAS  Google Scholar 

  7. Jenuwein, T. & Allis, C.D. Science 293, 1074–1080 (2001).

    Article  CAS  Google Scholar 

  8. Weake, V.M. & Workman, J.L. Mol. Cell 29, 653–663 (2008).

    Article  CAS  Google Scholar 

  9. Kim, J. et al. Cell 137, 459–471 (2009).

    Article  CAS  Google Scholar 

  10. McGinty, R., Kim, J., Chatterjee, C., Roeder, R. & Muir, T. Nature 453, 812–816 (2008).

    Article  CAS  Google Scholar 

  11. Okada, Y. et al. Cell 121, 167–178 (2005).

    Article  CAS  Google Scholar 

  12. Zhu, B. et al. Mol. Cell 20, 601–611 (2005).

    Article  CAS  Google Scholar 

  13. Chatterjee, C., McGinty, R.K., Pellois, J.P. & Muir, T.W. Angew. Chem. Int. Edn Engl. 46, 2814–2818 (2007).

    Article  CAS  Google Scholar 

  14. Van Kasteren, S.I. et al. Nature 446, 1105–1109 (2007).

    Article  CAS  Google Scholar 

  15. Simon, M. et al. Cell 128, 1003–1012 (2007).

    Article  CAS  Google Scholar 

  16. Luger, K., Mader, A.W., Richmond, R.K., Sargent, D.F. & Richmond, T.J. Nature 389, 251–260 (1997).

    Article  CAS  Google Scholar 

  17. Rabanal, F., DeGrado, W. & Dutton, P. Tetrahedr. Lett. 37, 1347–1350 (1996).

    Article  CAS  Google Scholar 

  18. Minsky, N. & Oren, M. Mol. Cell 16, 631–639 (2004).

    Article  CAS  Google Scholar 

  19. Geng, F. & Tansey, W.P. Mol. Biol. Cell 19, 3616–3624 (2008).

    Article  CAS  Google Scholar 

  20. McGinty, R.K. et al. ACS Chem. Biol. 4, 958–968 (2009).

    Article  CAS  Google Scholar 

  21. Whitby, F.G., Xia, G., Pickart, C.M. & Hill, C.P. J. Biol. Chem. 273, 34983–34991 (1998).

    Article  CAS  Google Scholar 

  22. Ramelot, T.A. et al. J. Struct. Funct. Genomics 4, 25–30 (2003).

    Article  CAS  Google Scholar 

  23. Hicke, L. Nat. Rev. Mol. Cell Biol. 2, 195–201 (2001).

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge J. Fernandez, L. Miller and R. Angeletti for assistance with ESI-MS analysis. We thank J. Kim and R. Subramanian for help in preparing hDot1 and M. Pratt for stimulating discussions. This work was funded by the US National Institutes of Health (grant number RC2CA148354) and the Starr Cancer Consortium. B.F. was supported by the Novartis and Swiss National Science Foundations. R.K.M. was supported by a US National Institutes of Health Medical Scientist Training Program grant.

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Authors and Affiliations

  1. Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York, USA

    Champak Chatterjee, Robert K McGinty, Beat Fierz & Tom W Muir

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  1. Champak Chatterjee
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  2. Robert K McGinty
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  3. Beat Fierz
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Contributions

C.C. and T.W.M. designed the experiments. C.C. performed the experiments. C.C., R.K.M. and B.F. prepared new reagents. C.C. and T.W.M. analyzed the experimental results and wrote the manuscript.

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Correspondence to Tom W Muir.

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The authors declare no competing financial interests.

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Supplementary Methods and Supplementary Figures 1–18 (PDF 5450 kb)

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Chatterjee, C., McGinty, R., Fierz, B. et al. Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation. Nat Chem Biol 6, 267–269 (2010). https://doi.org/10.1038/nchembio.315

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