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学術論文

Methylation of K9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome.

MPS-Authors
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Munari,  F.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Soeroes,  S.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Schomburg,  A.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Kost,  N.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

Schröder,  S.
Research Group of Biomolecular Spectroscopy and Single-Molecule Detection, MPI for biophysical chemistry, Max Planck Society;

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Rezaei-Ghaleh,  N.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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Stützer,  A.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Gelato,  K. A.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Walla,  P. J.
Research Group of Biomolecular Spectroscopy and Single-Molecule Detection, MPI for biophysical chemistry, Max Planck Society;

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Becker,  S.
Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society;

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Schwarzer,  D.
Research Group of Reaction Dynamics, MPI for biophysical chemistry, Max Planck Society;

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Fischle,  W.
Research Group of Chromatin Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Zweckstetter,  M.
Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society;

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フルテキスト (公開)

1539277.pdf
(出版社版), 3MB

付随資料 (公開)

1539277_Supplement_1.pdf
(付録資料), 3MB

引用

Munari, F., Soeroes, S., Zenn, H. M., Schomburg, A., Kost, N., Schröder, S., Klingberg, R., Rezaei-Ghaleh, N., Stützer, A., Gelato, K. A., Walla, P. J., Becker, S., Schwarzer, D., Zimmermann, B., Fischle, W., & Zweckstetter, M. (2012). Methylation of K9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1β with the nucleosome. Journal of Biological Chemistry, 287(40), 33756-33765. doi:10.1074/jbc.M112.390849.


引用: https://hdl.handle.net/11858/00-001M-0000-000F-EBAF-E
要旨
Binding of heterochromatin protein 1 (HP1) to the histone H3 lysine 9 trimethylation (H3K9me3) mark is a hallmark of establishment and maintenance of heterochromatin. Although genetic and cell biological aspects have been elucidated, the molecular details of HP1 binding to H3K9me3 nucleosomes are unknown. Using a combination of NMR spectroscopy and biophysical measurements on fully defined recombinant experimental systems, we demonstrate that H3K9me3 works as an on/off switch regulating distinct binding modes of hHP1β to the nucleosome. The methyl-mark determines a highly flexible and very dynamic interaction of the chromodomain of hHP1β with the H3-tail. There are no other constraints of interaction or additional multimerization interfaces. In contrast, in the absence of methylation, the hinge region and the N-terminal tail form weak nucleosome contacts mainly with DNA. In agreement with the high flexibility within the hHP1β-H3K9me3 nucleosome complex, the chromoshadow domain does not provide a direct binding interface. Our results report the first detailed structural analysis of a dynamic protein-nucleosome complex directed by a histone modification and provide a conceptual framework for understanding similar interactions in the context of chromatin.