Zhang Jing, Zhang Yan, You Qinglong, Huang Chang, Zhang Tiantian, Wang Mingzhu, Zhang Tianwei, Yang Xiaocheng, Xiong Jun, Li Yingfeng, Liu Chao-Pei, Zhang Zhuqiang, Xu Rui-Ming, Zhu Bing
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Science. 2022 Mar 4;375(6584):1053-1058. doi: 10.1126/science.abm0730. Epub 2022 Feb 10.
Bivalent genes are ready for activation upon the arrival of developmental cues. Here, we report that BEND3 is a CpG island (CGI)-binding protein that is enriched at regulatory elements. The cocrystal structure of BEND3 in complex with its target DNA reveals the structural basis for its DNA methylation-sensitive binding property. Mouse embryos ablated of died at the pregastrulation stage. null embryonic stem cells (ESCs) exhibited severe defects in differentiation, during which hundreds of CGI-containing bivalent genes were prematurely activated. BEND3 is required for the stable association of polycomb repressive complex 2 (PRC2) at bivalent genes that are highly occupied by BEND3, which suggests a reining function of BEND3 in maintaining high levels of H3K27me3 at these bivalent genes in ESCs to prevent their premature activation in the forthcoming developmental stage.
双价基因在发育信号到来时即准备好被激活。在此，我们报告BEND3是一种CpG岛（CGI）结合蛋白，在调控元件处富集。BEND3与其靶DNA形成的共晶体结构揭示了其对DNA甲基化敏感的结合特性的结构基础。敲除 的小鼠胚胎在原肠胚形成前阶段死亡。 缺失的胚胎干细胞（ESC）在分化过程中表现出严重缺陷，在此期间数百个含CGI的双价基因被过早激活。对于BEND3高度占据的双价基因，BEND3是多梳抑制复合物2（PRC2）在其上稳定结合所必需的，这表明BEND3在维持胚胎干细胞中这些双价基因高水平的H3K27me3以防止其在即将到来的发育阶段过早激活方面具有调控作用。
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