BMP4 resets mouse epiblast stem cells to naive pluripotency through ZBTB7A/B-mediated chromatin remodelling

作者：Yu, Shengyong; Zhou, Chunhua; Cao, Shangtao; He, Jiangping; Cai, Baomei; Wu, Kaixin; Qin, Yue; Huang, Xingnan; Xiao, Lizhan; Ye, Jing; Xu, Shuyang; Xie, Wenxiu; Kuang, Junqi; Chu, Shilong; Guo, Jing; Liu, He; Pang, Wei; Guo, Lin; Zeng, Mengying; Wang, Xiaoshan; Luo, Rongping; Li, Chen; Zhao, Guoqing; Wang, Bo; Wu, Linlin; Chen, Jiekai; Liu, Jing; Pei, Duanqing

来源：Nature Cell Biology, 2020, 22(6): 651-+.

DOI：10.1038/s41556-020-0516-x

• GROUND-STATE
• SELF-RENEWAL
• ACCESSIBILITY DYNAMICS
• TRANSITION
• GENERATION
• INDUCTION
• PATHWAYS
• TARGET
• GENE
• KLF4

BMP4 regulates a plethora of developmental processes, including the dorsal-ventral axis and neural patterning. Here, we report that BMP4 reconfigures the nuclear architecture during the primed-to-naive transition (PNT). We first established a BMP4-driven PNT and show that BMP4 orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a and Zbtb7b (Zbtb7a/b) as targets that drive PNT. ZBTB7A/B in turn facilitate the opening of naive pluripotent chromatin loci and the activation of nearby genes. Mechanistically, ZBTB7A not only binds to chromatin loci near to the genes that are activated, but also strategically occupies those that are silenced, consistent with a role of BMP4 in both activating and suppressing gene expression during PNT at the chromatin level. Our results reveal a previously unknown function of BMP4 in regulating nuclear architecture and link its targets ZBTB7A/B to chromatin remodelling and pluripotent fate control.
Yu, Zhou, Cao, He et al. show that BMP4 reconfigures the nuclear architecture during the transition from primed to naive pluripotency by targeting Zbtb7a and Zbtb7b, which encode proteins that mediate the opening of naive chromatin loci.

• 出版日期2020-6
• 单位中国科学院; 中国科学院广州生物医药与健康研究院; 中国科学院大学; 广州医科大学