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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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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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