Double chromodomains cooperate to recognize the methylated histone H3 tail

Article metrics

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1

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

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. 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)

  9. 9

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

  10. 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)

  11. 11

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

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 16

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

  17. 17

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

  18. 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)

  19. 19

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

  20. 20

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

  21. 21

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

  22. 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)

  23. 23

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

  24. 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)

  25. 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)

  26. 26

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

  27. 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)

  28. 28

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

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.

Author information

Correspondence to Fraydoon Rastinejad or Sepideh Khorasanizadeh.

Ethics declarations

Competing interests

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.

Supplementary information

Supplementary Notes

This file contains Supplementary Figures 1 and 2, and Supplementary Tables 1 and 2. (DOC 728 kb)

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.