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

    研究成果: Article査読

    79 被引用数 (Scopus)

    抄録

    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.

    本文言語English
    ページ(範囲)385-397.e8
    ジャーナルMolecular Cell
    69
    3
    DOI
    出版ステータスPublished - 2018 2 1

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

    フィンガープリント 「Structural Basis of Heterochromatin Formation by Human HP1」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

    引用スタイル