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Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor

Abstract

The lysine demethylase JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences (H3K4me3 and H4K20me3) through its tudor domains. Here we show using X-ray crystallography and calorimetry that H3K4me3 and H4K20me3, which are recognized with similar affinities by JMJD2A, adopt radically different binding modes, to the extent that we were able to design single point mutations in JMJD2A that inhibited the recognition of H3K4me3 but not H4K20me3 and vice versa.

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Figure 1: Interaction of JMJD2A hybrid tudor domains with trimethylated histones H3 and H4 peptides.
Figure 2: Two different binding modes of JMJD2A hybrid tudor domains with H3K4me3 and H4K20me3 peptides.

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References

  1. Kouzarides, T. Cell 128, 693–705 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Selenko, P. et al. Nat. Struct. Biol. 8, 27–31 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Jacobs, S.A. & Khorasanizadeh, S. Science 295, 2080–2083 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Nielsen, P.R. et al. Nature 416, 103–107 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Flanagan, J.F. et al. Nature 438, 1181–1185 (2005).

    Article  CAS  PubMed  Google Scholar 

  6. Huang, Y., Fang, J., Bedford, M.T., Zhang, Y. & Xu, R.M. Science 312, 748–751 (2006).

    Article  CAS  PubMed  Google Scholar 

  7. Botuyan, M.V. et al. Cell 127, 1361–1373 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li, H. et al. Nature 442, 91–95 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pena, P.V. et al. Nature 442, 100–103 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim, J. et al. EMBO Rep. 7, 397–403 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Shin, S. & Janknecht, R. Biochem. Biophys. Res. Commun. 353, 973–977 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Whetstine, J.R. et al. Cell 125, 467–481 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Klose, R.J. et al. Nature 442, 312–316 (2006).

    Article  CAS  PubMed  Google Scholar 

  14. Chen, Z. et al. Cell 125, 691–702 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. Ng, S.S. et al. Nature 448, 87–91 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Couture, J.F., Collazo, E., Ortiz-Tello, P.A., Brunzelle, J.S. & Trievel, R.C. Nat. Struct. Mol. Biol. 14, 689–695 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Chen, Z. et al. Proc. Natl. Acad. Sci. USA 104, 10818–10823 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We acknowledge the use of beamlines 19BM and 19ID at Argonne National Laboratory's Advance Photon Source (APS). We thank Y. Kim and C. Chang at APS for their assistance with X-ray data collection. Use of Argonne National Laboratory Structural Biology Center beamlines at APS is supported by the US Department of Energy, Office of Biological and Environmental Research under contract DE-AC02-06CH11357. This work was supported by grants from the Human Frontier Science Program and from the US National Institutes of Health (CA109449) to G.M.

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Correspondence to Georges Mer.

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Supplementary Figures 1 and 2, Supplementary Table 1, Supplementary Methods (PDF 3064 kb)

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Lee, J., Thompson, J., Botuyan, M. et al. Distinct binding modes specify the recognition of methylated histones H3K4 and H4K20 by JMJD2A-tudor. Nat Struct Mol Biol 15, 109–111 (2008). https://doi.org/10.1038/nsmb1326

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