研究人员报告了BEND3是一个富含调控元件的CpG岛（CGI）结合蛋白。BEND3与其目标DNA复合物的共晶体结构揭示了其DNA甲基化敏感结合特性的结构基础。敲除Bend3的小鼠胚胎在孕前阶段死亡。Bend3无效的ES细胞在分化中表现出严重的缺陷，在分化过程中，数百个含CGI的二价基因被过早激活。BEND3需要PRC2复合物在BEND3高度占据的二价基因上稳定结合，这表明BEND3在ES细胞中维持这些二价基因高水平的H3K27me3，以防止它们在即将到来的发育阶段被过早激活。
据悉，二价基因在发育线索到来时准备被激活。
附：英文原文
Title: Highly enriched BEND3 prevents the premature activation of bivalent genes during differentiation
Author: Jing Zhang, Yan Zhang, Qinglong You, Chang Huang, Tiantian Zhang, Mingzhu Wang, Tianwei Zhang, Xiaocheng Yang, Jun Xiong, Yingfeng Li, Chao-Pei Liu, Zhuqiang Zhang, Rui-Ming Xu, Bing Zhu
Issue&Volume: 2022-02-10
Abstract: Bivalent genes are ready for activation upon the arrival of developmental cues. Here we report that BEND3 is a CpG island (CGI) binding protein enriched at regulatory elements. The cocrystal structure of BEND3 in complex with its target DNA revealed the structural basis for its DNA methylation-sensitive binding property. Mouse embryos ablated of Bend3 died at pre-gastrulation stage. Bend3 null ES cells exhibited severe defects in differentiation, during which hundreds of CGI-containing bivalent genes were prematurely activated. BEND3 is required for stable association of PRC2 complex at bivalent genes that are highly occupied by BEND3, suggesting a reining function of BEND3 in maintaining high level of H3K27me3 at these bivalent genes in ES cells to prevent them from premature activation in the forthcoming developmental stage.
DOI: abm0730
Source: https://www.science.org/doi/10.1126/science.abm0730