Structural Basis of Heterochromatin Formation by Human HP1

Shinichi Machida, Yoshimasa Takizawa, Masakazu Ishimaru, Yukihiko Sugita, Satoshi Sekine, Jun ichi Nakayama, Matthias Wolf, Hitoshi Kurumizaka

    Research output: Contribution to journalArticle

    52 Citations (Scopus)

    Abstract

    Heterochromatin plays important roles in transcriptional silencing and genome maintenance by the formation of condensed chromatin structures, which determine the epigenetic status of eukaryotic cells. The trimethylation of histone H3 lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of heterochromatin formation. However, the mechanism by which HP1 folds chromatin-containing H3K9me3 into a higher-order structure has not been elucidated. Here we report the three-dimensional structure of the H3K9me3-containing dinucleosomes complexed with human HP1α, HP1β, and HP1γ, determined by cryogenic electron microscopy with a Volta phase plate. In the structures, two H3K9me3 nucleosomes are bridged by a symmetric HP1 dimer. Surprisingly, the linker DNA between the nucleosomes does not directly interact with HP1, thus allowing nucleosome remodeling by the ATP-utilizing chromatin assembly and remodeling factor (ACF). The structure depicts the fundamental architecture of heterochromatin. HP1 and H3 Lys9 trimethylations (H3K9me3) are hallmarks of heterochromatin, and they play pivotal roles in the epigenetic propagation of heterochromatin. Machida et al. describe the structure of the H3K9me3-containing dinucleosome complexed with human HP1, obtained by the cryo-EM technique.

    Original languageEnglish
    Pages (from-to)385-397.e8
    JournalMolecular Cell
    Volume69
    Issue number3
    DOIs
    Publication statusPublished - 2018 Feb 1

    Keywords

    • ACF
    • chromatin
    • cryo-EM
    • epigenetics
    • H3K9me3
    • heterochromatin
    • histone
    • HP1
    • nucleosome

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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  • Cite this

    Machida, S., Takizawa, Y., Ishimaru, M., Sugita, Y., Sekine, S., Nakayama, J. I., Wolf, M., & Kurumizaka, H. (2018). Structural Basis of Heterochromatin Formation by Human HP1. Molecular Cell, 69(3), 385-397.e8. https://doi.org/10.1016/j.molcel.2017.12.011