Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Molecular Cryo-Electron Microscopy Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa 904-0495, Japan.
Mol Cell. 2018 Feb 1;69(3):385-397.e8. doi: 10.1016/j.molcel.2017.12.011. Epub 2018 Jan 11.
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.
异染色质通过形成浓缩的染色质结构在转录沉默和基因组维护中发挥重要作用，决定真核细胞的表观遗传状态。组蛋白 H3 赖氨酸 9（H3K9me3）的三甲基化是异染色质形成的标志，异染色质蛋白 1（HP1）的靶标。然而，HP1 将含有 H3K9me3 的染色质折叠成更高阶结构的机制尚未阐明。在这里，我们通过低温电子显微镜和 Volta 相衬技术报告了与人 HP1α、HP1β 和 HP1γ 结合的含 H3K9me3 的二聚核小体复合物的三维结构。在这些结构中，两个 H3K9me3 核小体由对称的 HP1 二聚体桥接。令人惊讶的是，核小体之间的连接 DNA 不会直接与 HP1 相互作用，从而允许利用 ATP 的染色质组装和重塑因子 (ACF) 进行核小体重塑。该结构描绘了异染色质的基本结构。
