在高等哺乳动物中，染色质的高级结构及其动态调节对很多关键生物功能的正常行使具有重要的作用。目前已知的影响染色质高级结构的染色质架构蛋白数量不多，且只能从一定程度上部分地解释染色质的结构和动态变化，亟需发现新的染色质架构相关的调控蛋白。我们发现BEND3可以特异地与非甲基化DNA结合，并通过预实验发现其主要结合在基因组的CpG岛区域。进一步解析BEND3关键识别结构域和DNA的共结晶蛋白结构，我们发现BEND3可以二聚体形式存在并同时结合两分子的DNA序列。这提示我们BEND3很可能同时结合两个远距离的CpG岛，介导多基因的启动子-启动子相互作用。本项目计划系统地研究BEND3结合非甲基化DNA的生化及结构机理，分析BEND3结合染色质与染色质状态的相互关系及其对基因转录的影响，重点研究BEND3对胚胎干细胞诱导分化过程中染色质相互作用的动态调节，阐明BEND3在染色质高级结构中的功能。

The regulation of high order structure of mammalian chromatin is critical for many important biological functions. A few known chromatin architecture proteins can only partially explain chromatin high order structure on a limited extent, which makes it necessary to identify new key players and elaborate their functions. We’ve identified BEND3 as a novel unmethylated DNA binding protein and found it’s mainly localized within unmethylated CpG islands in our early work. Co-crystal structure of key domain of BEND3 and its binding motif shows BEND3 can form dimer which thereafter binds to two copies of DNA motifs. This suggests that BEND3 potentially interacts with two distal CpG islands and mediates long range promoter-promoter interactions. In this project, we are planning to systematically study the mechanisms of the recognition of BEND3 for unmethylated DNA, the relationship between BEND3 binding and chromatin states, and especially the role that BEND3 plays in the regulation of chromatin high order structure during ES cell differentiation.