Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding.
Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding.
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DOI：
10.1016/j.molcel.2018.01.039
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发表时间：
2018-03-01
期刊：
影响因子：
16
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Chen S;Jiao L;Shubbar M;Yang X;Liu X
发育调节的附属亚基决定了PRC2的功能。在这里，我们报道了由Suz12、Rbbp4、Jarid2和Aebp2片段组成的120 KDa异四聚体复合体的晶体结构，以及Suz12和Rbbp4的无效二元复合体。Suz12包含两个独特的结构平台，它们定义了不同类别的PRC2全息复合物用于染色质结合。Aebp2和Phf19竞争结合Suz12的非规范C2结构域；Jarid2和eop占据PrC2染色质结合所需的重叠Suz12表面。Suz12和Aebp2逐渐阻断组蛋白H3K4与Rbbp4的结合，提示Rbbp4可能不直接参与活性H3K4me3组蛋白标记对PRC2的抑制。Jarid2和Aebp2实现的核小体结合部分是由这些结构引起的，这也揭示了Jarid2-Suz12相互作用的中断可能是Suz12致癌染色体易位的发病机制。
Developmentally regulated accessory subunits dictate PRC2 function. Here, we report the crystal structures of a 120KDa heterotetrameric complex consisting of Suz12, Rbbp4, Jarid2 and Aebp2 fragments that is minimally active in nucleosome binding, and of an inactive binary complex of Suz12 and Rbbp4. Suz12 contains two unique structural platforms that define distinct classes of PRC2 holo complexes for chromatin binding. Aebp2 and Phf19 compete for binding of a noncanonical C2 domain of Suz12; Jarid2 and EPOP occupy an overlapped Suz12 surface required for chromatin association of PRC2. Suz12 and Aebp2 progressively block histone H3K4 binding to Rbbp4, suggesting that Rbbp4 may not be directly involved in PRC2 inhibition by the active H3K4me3 histone mark. Nucleosome binding enabled by Jarid2 and Aebp2 is in part accounted for by the structures, which also reveal that disruption of the Jarid2–Suz12 interaction may underlie the disease mechanism of an oncogenic chromosomal translocation of Suz12.
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影响因子：
7.7
作者：
Ciferri C;Lander GC;Maiolica A;Herzog F;Aebersold R;Nogales E
通讯作者：
Nogales E
影响因子：
16.6
作者：
Justin N;Zhang Y;Tarricone C;Martin SR;Chen S;Underwood E;De Marco V;Haire LF;Walker PA;Reinberg D;Wilson JR;Gamblin SJ
通讯作者：
Gamblin SJ
DOI：
10.1073/pnas.101132598
发表时间：
2001-05-22
影响因子：
11.1
作者：
Koontz, JI;Soreng, AL;Sklar, J
通讯作者：
Sklar, J
影响因子：
16
作者：
Cao, R;Zhang, Y
通讯作者：
Zhang, Y
影响因子：
10.5
作者：
Li, Gang;Margueron, Raphael;Reinberg, Danny
通讯作者：
Reinberg, Danny