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Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain

Nature Structural & Molecular Biology volume 17, pages 1027–1029 (2010)Cite this article

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Abstract

MSL3 resides in the MSL (male-specific lethal) complex, which upregulates transcription by spreading the histone H4 Lys16 (H4K16) acetyl mark. We discovered a DNA-dependent interaction of MSL3 chromodomain with the H4K20 monomethyl mark. The structure of a ternary complex shows that the DNA minor groove accommodates the histone H4 tail, and monomethyllysine inserts in a four-residue aromatic cage in MSL3. H4K16 acetylation antagonizes MSL3 binding, suggesting that MSL function is regulated by a combination of post-translational modifications.

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Figure 1: MSL3 chromodomain structure and specificity.
Figure 2: Structure of the MSL3 chromodomain in complex with DNA and the H4K20me1 peptide.

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Acknowledgements

We thank K. Clines and M. Chruszcz for technical support and T. Conrad and A. Akhtar for initiating biological investigations. This work was supported by grants from the US National Institutes of Health (GM070558) and the American Heart Association (0740058N) to S.K.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Virginia Health System, Charlottesville, Virginia, USA

    Daesung Kim, Bartlomiej J Blus, Fraydoon Rastinejad & Sepideh Khorasanizadeh

  2. Department of Pharmacology, University of Virginia Health System, Charlottesville, Virginia, USA

    Vikas Chandra, Pengxiang Huang & Fraydoon Rastinejad

  3. Center for Molecular Design, University of Virginia Health System, Charlottesville, Virginia, USA

    Fraydoon Rastinejad

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  1. Daesung Kim
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  2. Bartlomiej J Blus
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Contributions

D.K., B.J.B. and S.K. designed, performed and analyzed experiments; V.C. assisted with DNA purification and mutagenesis; F.R. and P.H. assisted with crystallography; B.J.B. and S.K. wrote the paper.

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Correspondence to Sepideh Khorasanizadeh.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Tables 1 and 2 and Supplementary Figures 1–4 (PDF 3435 kb)

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Kim, D., Blus, B., Chandra, V. et al. Corecognition of DNA and a methylated histone tail by the MSL3 chromodomain. Nat Struct Mol Biol 17, 1027–1029 (2010). https://doi.org/10.1038/nsmb.1856

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