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Double chromodomains cooperate to recognize the methylated histone H3 tail

Nature volume 438, pages 1181–1185 (2005)Cite this article

Abstract

Chromodomains are modules implicated in the recognition of lysine-methylated histone tails and nucleic acids1,2. CHD (for chromo-ATPase/helicase-DNA-binding) proteins regulate ATP-dependent nucleosome assembly and mobilization through their conserved double chromodomains and SWI2/SNF2 helicase/ATPase domain3,4,5. The Drosophila CHD1 localizes to the interb

ands and puffs of the polytene chromosomes, which are classic sites of transcriptional activity6. Other CHD isoforms (CHD3/4 or Mi-2) are important for nucleosome remodelling in histone deacetylase complexes7,8. Deletion of chromodomains impairs nucleosome binding and remodelling by CHD proteins4. Here we describe the structure of the tandem arrangement of the human CHD1 chromodomains, and its interactions with histone tails. Unlike HP1 and Polycomb proteins that use single chromodomains to bind to their respective methylated histone H3 tails, the two chromodomains of CHD1 cooperate to interact with one methylated H3 tail. We show that the human CHD1 double chromodomains target the lysine 4-methylated histone H3 tail (H3K4me), a hallmark of active chromatin9. Methylammonium recognition involves two aromatic residues, not the three-residue aromatic cage used by chromodomains of HP1 and Polycomb proteins10,11,12,13. Furthermore, unique inserts within chromodomain 1 of CHD1 block the expected site of H3 tail binding seen in HP1 and Polycomb, instead directing H3 binding to a groove at the inter-chromodomain junction.

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Figure 1: Structure of human CHD1 double chromodomains.
Figure 2: Peptide selectivity of the human CHD1 double chromodomains.
Figure 3: Methyllysine binding by human CHD1.
Figure 4: Comparison of CHD1 with HP1 and Polycomb.

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References

  1. Brehm, A., Tufteland, K. R., Aasland, R. & Becker, P. B. The many colours of chromodomains. BioEssays 26, 133–140 (2004)

    Article  CAS  Google Scholar 

  2. Tajul-Arifin, K., Teasdale, R., Ravasi, T., Hume, D. A. & Mattick, J. S. Identification and analysis of chromodomain-containing proteins encoded in the mouse transcriptome. Genome Res. 13, 1416–1429 (2003)

    Article  CAS  Google Scholar 

  3. Lusser, A., Urwin, D. L. & Kadonaga, J. T. Distinct activities of CHD1 and ACF in ATP-dependent chromatin assembly. Nature Struct. Mol. Biol. 12, 160–166 (2005)

    Article  CAS  Google Scholar 

  4. Bouazoune, K. et al. The dMi-2 chromodomains are DNA binding modules important for ATP-dependent nucleosome mobilization. EMBO J. 21, 2430–2440 (2002)

    Article  CAS  Google Scholar 

  5. Woodage, T., Basrai, M. A., Baxevanis, A. D., Hieter, P. & Collins, F. S. Characterization of the CHD family of proteins. Proc. Natl Acad. Sci. USA 94, 11472–11477 (1997)

    Article  ADS  CAS  Google Scholar 

  6. Stokes, D. G., Tartof, K. D. & Perry, R. P. CHD1 is concentrated in interbands and puffed regions of Drosophila polytene chromosomes. Proc. Natl Acad. Sci. USA 93, 7137–7142 (1996)

    Article  ADS  CAS  Google Scholar 

  7. Tong, J. K., Hassig, C. A., Schnitzler, G. R., Kingston, R. E. & Schreiber, S. L. Chromatin deacetylation by an ATP-dependent nucleosome remodelling complex. Nature 395, 917–921 (1998)

    Article  ADS  CAS  Google Scholar 

  8. Zhang, Y., LeRoy, G., Seelig, H. P., Lane, W. S. & Reinberg, D. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell 95, 279–289 (1998)

    Article  CAS  Google Scholar 

  9. Schneider, R. et al. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nature Cell Biol. 6, 73–77 (2004)

    Article  CAS  Google Scholar 

  10. Jacobs, S. A. & Khorasanizadeh, S. Structure of the HP1 chromodomain bound to a lysine 9-methylated histone H3 tail. Science 295, 2080–2083 (2002)

    Article  ADS  CAS  Google Scholar 

  11. Nielsen, P. R. et al. Structure of the HP1 chromodomain bound to histone H3 methylated at lysine 9. Nature 416, 103–107 (2002)

    Article  ADS  CAS  Google Scholar 

  12. Fischle, W. et al. Molecular basis for the discrimination of repressive methyl-lysine marks in histone H3 by Polycomb and HP1 chromodomains. Genes Dev. 17, 1870–1881 (2003)

    Article  CAS  Google Scholar 

  13. Min, J., Zhang, Y. & Xu, R. M. Structural basis for specific binding of Polycomb chromodomain to histone H3 methylated at Lys 27. Genes Dev. 17, 1823–1828 (2003)

    Article  CAS  Google Scholar 

  14. Pray-Grant, M. G., Daniel, J. A., Schieltz, D., Yates, J. R. & Grant, P. A. Chd1 chromodomain links histone H3 methylation with SAGA- and SLIK-dependent acetylation. Nature 433, 434–438 (2005)

    Article  ADS  CAS  Google Scholar 

  15. Santos-Rosa, H. et al. Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. Mol. Cell 12, 1325–1332 (2003)

    Article  CAS  Google Scholar 

  16. Schurter, B. T. et al. Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry 40, 5747–5756 (2001)

    Article  CAS  Google Scholar 

  17. Kouskouti, A. & Talianidis, I. Histone modifications defining active genes persist after transcriptional and mitotic inactivation. EMBO J. 24, 347–357 (2005)

    Article  CAS  Google Scholar 

  18. Dai, J., Sultan, S., Taylor, S. S. & Higgins, J. M. The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment. Genes Dev. 19, 472–488 (2005)

    Article  CAS  Google Scholar 

  19. Stokes, D. G. & Perry, R. P. DNA-binding and chromatin localization properties of CHD1. Mol. Cell. Biol. 15, 2745–2753 (1995)

    Article  CAS  Google Scholar 

  20. Fischle, W., Wang, Y. & Allis, C. D. Binary switches and modification cassettes in histone biology and beyond. Nature 425, 475–479 (2003)

    Article  ADS  CAS  Google Scholar 

  21. Khorasanizadeh, S. The nucleosome: from genomic organization to genomic regulation. Cell 116, 259–272 (2004)

    Article  CAS  Google Scholar 

  22. Jacobson, R. H., Ladurner, A. G., King, D. S. & Tjian, R. Structure and function of a human TAFII250 double bromodomain module. Science 288, 1422–1425 (2000)

    Article  ADS  CAS  Google Scholar 

  23. Huyen, Y. et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 432, 406–411 (2004)

    Article  ADS  CAS  Google Scholar 

  24. Jacobs, S. A., Fischle, W. & Khorasanizadeh, S. Assays for the determination of structure and dynamics of the interaction of the chromodomain with histone peptides. Methods Enzymol. 376, 131–148 (2004)

    Article  CAS  Google Scholar 

  25. Brunger, A. T. et al. Crystallography and NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr. D 54, 905–921 (1998)

    Article  CAS  Google Scholar 

  26. DeLano, W. L. PyMOL User's Guide (DeLano Scientific, San Carlos, California, 2004)

    Google Scholar 

  27. Thoma, N. H. et al. Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nature Struct. Mol. Biol. 12, 350–356 (2005)

    Article  Google Scholar 

  28. Nicholls, A. GRASP: Graphical Representation and Analysis of Surface Properties (Columbia University, New York, 1993)

    Google Scholar 

Download references

Acknowledgements

We thank M. Zimmerman for assistance with diffraction data collection. This work was supported by grants from the National Institutes of Health (to S.K.). Author Contributions J.F.F. and L-Z.M. contributed equally to this work.

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Author notes

  1. Li-Zhi Mi

    Present address: Department of Pathology, Harvard Medical School and The CBR Institute for Biomedical Research, Inc., 200 Longwood Avenue, Boston, Massachusetts, 02115, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics,

    John F. Flanagan, Katrina L. Clines, Fraydoon Rastinejad & Sepideh Khorasanizadeh

  2. Department of Pharmacology,

    Li-Zhi Mi & Fraydoon Rastinejad

  3. Department of Molecular Physiology and Biological Physics, University of Virginia Health System, Virginia, 22908, Charlottesville, USA

    Maksymilian Chruszcz, Marcin Cymborowski & Wladek Minor

  4. Argonne National Laboratory, Biosciences Division/Structural Biology Center, Illinois, 60439, Argonne, USA

    Youngchang Kim

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Correspondence to Fraydoon Rastinejad or Sepideh Khorasanizadeh.

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The atomic coordinates have been deposited in the Protein Data Bank with the accession numbers 2B2Y, 2B2W, 2B2V, 2B2U and 2B2T. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Flanagan, J., Mi, LZ., Chruszcz, M. et al. Double chromodomains cooperate to recognize the methylated histone H3 tail. Nature 438, 1181–1185 (2005). https://doi.org/10.1038/nature04290

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