Zscan4 mediates ubiquitination and degradation of the corepressor complex to promote chromatin accessibility in 2C-like cells

• 成果类型: Article
• 署名作者: Yang, Jiao; Dan, Jiameng; Zhao, Nannan; Liu, Linlin; Wang, Huasong; Liu, Qiangqiang; Wang, Lingling; Li, Jie; Wu, Yiwei; Chen, Feilong; Fu, Weilun; Liu, Fei; Lin, Meiqi; Zhang, Weiyu; Chen, Fuquan; Liu, Xinqi; Lu, Xinyi; Chen, Quan; Wu, Xudong; Niu, Yuyu; Yang, Na; Zhu, Yushan; Long, Jiafu; Liu, Lin
• 署名单位: Nankai University; Nankai University; Kunming University of Science & Technology; Chinese Academy of Medical Sciences - Peking Union Medical College; Peking Union Medical College; Nankai University; Nankai University; Tianjin Medical University; Nankai University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11793
• DOI: 10.1073/pnas.2407490121
• 发表日期: 2024-12-24
• 关键词: zygotic genome activation; embryonic-like cells; telomere elongation; gene-expression; mouse oocytes; stem-cells; reveals; h3k4me3; landscape; heterochromatin

摘要

Zygotic genome activation occurs in two-cell (2C) embryos, and a 2C-like state is also activated in sporadic (similar to 1%) naive embryonic stem cells in mice. Elevated chromatin accessibility is critical for the 2C-like state to occur, yet the underlying molecular mechanisms remain elusive. Zscan4 exhibits burst expression in 2C embryos and 2C-like cells. Here, we show that Zscan4 mediates chromatin remodeling to promote the chromatin accessibility for achieving the 2C-like state. Through coimmunoprecipitation/mass spectrometry, we identified that Zscan4 interacts with the corepressors Kap1/Trim28, Lsd1, and Hdac1, also with H3K9me3 modifiers Suv39h1/2, to transiently form a repressive chromatin complex. Then, Zscan4 mediates the degradation of these chromatin repressors by recruiting Trim25 as an E3 ligase, enabling the ubiquitination of Lsd1, Hdac1, and Suv39h1/2. Degradation of the chromatin repressors promotes the chromatin accessibility for activation of the 2C-like state. These findings reveal the molecular insights into the roles of Zscan4 in promoting full activation of the 2C-like state.-