Zscan4 mediates ubiquitination and degradation of the corepressor complex to promote chromatin accessibility in 2C-like cells
Zygotic genome activation occurs in two-cell (2C) embryos, and a 2C-like state is also activated in sporadic (~1%) naïve 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.
Authors
- Xudong Wu (ORCID: https://orcid.org/0000-0001-9594-479X)
- Quan Chen (ORCID: https://orcid.org/0000-0001-7539-8728)
- Lin Liu (ORCID: https://orcid.org/0000-0001-9881-6830)
- Linlin Liu (ORCID: https://orcid.org/0009-0002-2688-4492)
- Weilun Fu (ORCID: https://orcid.org/0000-0002-2540-7961)
- Yushan Zhu (ORCID: https://orcid.org/0000-0002-5648-0416)
- Huasong Wang
- Xinyi Lu (ORCID: https://orcid.org/0000-0002-3885-3960)
- Jiao Yang
- Jiameng Dan (ORCID: https://orcid.org/0009-0009-9178-881X)
- Yuyu Niu (ORCID: https://orcid.org/0000-0002-8797-4152)
- Jiafu Long (ORCID: https://orcid.org/0000-0002-6625-0147)
- Feilong Chen (ORCID: https://orcid.org/0000-0002-6678-4966)
- Lingling Wang (ORCID: https://orcid.org/0000-0002-1049-9170)
- Jie Li (ORCID: https://orcid.org/0000-0003-3902-642X)
- Nannan Zhao (ORCID: https://orcid.org/0000-0002-7546-2088)
- Weiyu Zhang
- Na Yang (ORCID: https://orcid.org/0000-0002-6956-6630)
- Xinqi Liu (ORCID: https://orcid.org/0000-0002-6045-718X)
- Fuquan Chen (ORCID: https://orcid.org/0000-0002-0538-2648)
- Meiqi Lin (ORCID: https://orcid.org/0009-0007-5828-9360)
- Qiangqiang Liu (ORCID: https://orcid.org/0000-0002-7542-2465)
- Fei Liu (ORCID: https://orcid.org/0000-0002-7848-5226)
- Yiwei Wu (ORCID: https://orcid.org/0009-0001-1246-1192)
Institutions
- Kunming University of Science and Technology (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Nankai University (CN)
- Yunnan Yingmao Biotechnology (China) (CN)
- Tianjin Medical University (CN)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1073/pnas.2407490121
- Citations
- 9
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 2.10
Funders
- National Natural Science Foundation of China