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

    36 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

    Fingerprint

    Heterochromatin
    Nucleosomes
    Chromatin Assembly and Disassembly
    Epigenomics
    Chromatin
    heterochromatin-specific nonhistone chromosomal protein HP-1
    Eukaryotic Cells
    Histones
    Lysine
    Electron Microscopy
    Adenosine Triphosphate
    Maintenance
    Genome
    DNA

    Keywords

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

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    Cite this

    Machida, S., Takizawa, Y., Ishimaru, M., Sugita, Y., Sekine, S., Nakayama, J. I., ... 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

    Structural Basis of Heterochromatin Formation by Human HP1. / Machida, Shinichi; Takizawa, Yoshimasa; Ishimaru, Masakazu; Sugita, Yukihiko; Sekine, Satoshi; Nakayama, Jun ichi; Wolf, Matthias; Kurumizaka, Hitoshi.

    In: Molecular Cell, Vol. 69, No. 3, 01.02.2018, p. 385-397.e8.

    Research output: Contribution to journalArticle

    Machida, S, Takizawa, Y, Ishimaru, M, Sugita, Y, Sekine, S, Nakayama, JI, Wolf, M & Kurumizaka, H 2018, 'Structural Basis of Heterochromatin Formation by Human HP1', Molecular Cell, vol. 69, no. 3, pp. 385-397.e8. https://doi.org/10.1016/j.molcel.2017.12.011
    Machida S, Takizawa Y, Ishimaru M, Sugita Y, Sekine S, Nakayama JI et al. Structural Basis of Heterochromatin Formation by Human HP1. Molecular Cell. 2018 Feb 1;69(3):385-397.e8. https://doi.org/10.1016/j.molcel.2017.12.011
    Machida, Shinichi ; Takizawa, Yoshimasa ; Ishimaru, Masakazu ; Sugita, Yukihiko ; Sekine, Satoshi ; Nakayama, Jun ichi ; Wolf, Matthias ; Kurumizaka, Hitoshi. / Structural Basis of Heterochromatin Formation by Human HP1. In: Molecular Cell. 2018 ; Vol. 69, No. 3. pp. 385-397.e8.
    @article{114682ed89e949bcad096baa21d8038c,
    title = "Structural Basis of Heterochromatin Formation by Human HP1",
    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.",
    keywords = "ACF, chromatin, cryo-EM, epigenetics, H3K9me3, heterochromatin, histone, HP1, nucleosome",
    author = "Shinichi Machida and Yoshimasa Takizawa and Masakazu Ishimaru and Yukihiko Sugita and Satoshi Sekine and Nakayama, {Jun ichi} and Matthias Wolf and Hitoshi Kurumizaka",
    year = "2018",
    month = "2",
    day = "1",
    doi = "10.1016/j.molcel.2017.12.011",
    language = "English",
    volume = "69",
    pages = "385--397.e8",
    journal = "Molecular Cell",
    issn = "1097-2765",
    publisher = "Cell Press",
    number = "3",

    }

    TY - JOUR

    T1 - Structural Basis of Heterochromatin Formation by Human HP1

    AU - Machida, Shinichi

    AU - Takizawa, Yoshimasa

    AU - Ishimaru, Masakazu

    AU - Sugita, Yukihiko

    AU - Sekine, Satoshi

    AU - Nakayama, Jun ichi

    AU - Wolf, Matthias

    AU - Kurumizaka, Hitoshi

    PY - 2018/2/1

    Y1 - 2018/2/1

    N2 - 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.

    AB - 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.

    KW - ACF

    KW - chromatin

    KW - cryo-EM

    KW - epigenetics

    KW - H3K9me3

    KW - heterochromatin

    KW - histone

    KW - HP1

    KW - nucleosome

    UR - http://www.scopus.com/inward/record.url?scp=85040448858&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85040448858&partnerID=8YFLogxK

    U2 - 10.1016/j.molcel.2017.12.011

    DO - 10.1016/j.molcel.2017.12.011

    M3 - Article

    AN - SCOPUS:85040448858

    VL - 69

    SP - 385-397.e8

    JO - Molecular Cell

    JF - Molecular Cell

    SN - 1097-2765

    IS - 3

    ER -