Structural Basis of Heterochromatin Formation by Human HP1

被引:190
作者
Machida, Shinichi [1 ]
Takizawa, Yoshimasa [2 ]
Ishimaru, Masakazu [1 ]
Sugita, Yukihiko [2 ]
Sekine, Satoshi [1 ]
Nakayama, Jun-ichi [3 ]
Wolf, Matthias [2 ]
Kurumizaka, Hitoshi [1 ,4 ]
机构
[1] Waseda Univ, Grad Sch Adv Sci & Engn, Lab Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan
[2] Okinawa Inst Sci & Technol Grad Univ, Mol Cryoelectron Microscopy Unit, 1919-1 Tancha, Onna Son, Okinawa 9040495, Japan
[3] Natl Inst Basic Biol, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan
[4] Waseda Univ, Inst Med Oriented Struct Biol, Shinjuku Ku, 2-2 Wakamatsu Cho, Tokyo 1628480, Japan
关键词
PARTICLE ELECTRON CRYOMICROSCOPY; HISTONE H3; CHROMATIN-STRUCTURE; CRYSTAL-STRUCTURE; PHASE-SEPARATION; MAMMALIAN-CELLS; LYSINE; 9; NUCLEOSOME; BINDING; PROTEINS;
D O I
10.1016/j.molcel.2017.12.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 HP1 alpha, HP1 beta, and HP1 gamma, 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.
引用
收藏
页码:385 / +
页数:21
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