Science, 10 February, 2022

Highly enriched BEND3 prevents the premature activation of bivalent genes during differentiation

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

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.

Article link：https://www.science.org/doi/10.1126/science.abm0730