The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure

Abstract

Histone methylation regulates chromatin function dependent on the site and degree of the modification. In addition to creating binding sites for proteins, methylated lysine residues are likely to influence chromatin structure directly. Here we present crystal structures of nucleosomes reconstituted with methylated histones and investigate the folding behavior of resulting arrays. We demonstrate that dimethylation of histone H3 at lysine residue 79 locally alters the nucleosomal surface, whereas trimethylation of H4 at lysine residue 20 affects higher-order structure.

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Figure 1: Crystal structures of nucleosomes containing H3Kc79me2 and H4Kc20me3.
Figure 2: Sedimentation velocity analysis of unmodified, H3Kc79Me2 and H4Kc20Me3 nucleosomal arrays.

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Acknowledgements

We thank S. Grigoryev (Pennsylvania State University) for the 601 template. This work was supported by a grant from the March of Dimes and the US National Institutes of Health (NIH; GM067777) to K.L., and by NIH grants EB001987 to K.M.S. and GM45916 to J.C.H. K.L. and K.M.S. are supported by the Howard Hughes Medical Institute.

Author information

X.L. carried out the crystallographic and array work; M.D.S. made the methylated histone analogues; J.V.C. helped with refinement and figure preparation; J.C.H., K.M.S. and K.L. supervised the work and wrote the manuscript.

Correspondence to Karolin Luger.

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Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Table 1 and Supplementary Methods (PDF 760 kb)

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Lu, X., Simon, M., Chodaparambil, J. et al. The effect of H3K79 dimethylation and H4K20 trimethylation on nucleosome and chromatin structure. Nat Struct Mol Biol 15, 1122–1124 (2008). https://doi.org/10.1038/nsmb.1489

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