Structures of human PRC2 with its cofactors AEBP2 and JARID2
Structures of human PRC2 with its cofactors AEBP2 and JARID2
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DOI：
10.1126/science.aar5700
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发表时间：
2018-02-23
期刊：
影响因子：
56.9
通讯作者：
Nogales, Eva
中科院分区：
文献类型：
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作者：
Kasinath, Vignesh;Faini, Marco;Nogales, Eva
由多梳抑制复合体2(PRC2)转录抑制组蛋白H3赖氨酸27甲基化是细胞分化和发育所必需的。在这里，我们报道了人PRC2的冷冻电子显微镜结构，在与其辅因子JARID2和AEBP2复合时，处于基础状态和两个不同的活性状态。这两个辅因子都模仿了组蛋白H3尾巴的结合。JARID2由PRC2甲基化，模仿甲基化的H3尾巴刺激PRC2活性，而AEBP2与RbAp48亚单位相互作用，模仿未修饰的H3尾巴。SuZ12与组装中的所有其他亚基相互作用，从而有助于复合体的稳定性。我们的分析定义了功能相关的PRC2的完整架构，并提供了一个结构框架来理解辅因子、组蛋白尾和RNA对其调控。
Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.