Structural Basis of Heterochromatin Formation by Human HP1
Structural Basis of Heterochromatin Formation by Human HP1
复制标题
人类 HP1 形成异染色质的结构基础
DOI：
10.1016/j.molcel.2017.12.011
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发表时间：
2018-02-01
期刊：
影响因子：
16
通讯作者：
Kurumizaka, Hitoshi
中科院分区：
文献类型：
--
作者：
Machida, Shinichi;Takizawa, Yoshimasa;Kurumizaka, Hitoshi
异染色质在转录沉默和基因组维持中起重要作用，它通过形成染色质浓缩结构，决定真核细胞的表观遗传状态。组蛋白H3赖氨酸9（H3 K9 me 3）的三甲基化是异染色质蛋白1（HP 1）的靶点，是异染色质形成的标志。然而，HP 1折叠含染色质的H3 K9 me 3成更高级结构的机制尚未阐明。在这里，我们报告的三维结构的H3 K9 me 3-含有dinucleosomes复杂的人HP 1 α，HP 1 β，HP 1 γ，确定通过低温电子显微镜与伏相板。在结构中，两个H3 K9 me 3核小体由对称的HP 1二聚体桥接。令人惊讶的是，核小体之间的接头DNA不直接与HP 1相互作用，从而允许核小体通过利用ATP的染色质组装和重塑因子（ACF）进行重塑。该结构描述了异染色质的基本结构。
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.