Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation
FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.
Authors
- Chuanhai Fu (ORCID: https://orcid.org/0000-0003-4354-3796)
- Shuaiyu Liu
- Olanrewaju Ayodeji Durojaye (ORCID: https://orcid.org/0000-0001-8988-8154)
- Bo Sun (ORCID: https://orcid.org/0000-0001-8419-9245)
- Xuebiao Yao (ORCID: https://orcid.org/0000-0001-8982-5911)
- Tahir Ullah (ORCID: https://orcid.org/0000-0003-1434-0498)
- Zhikai Wang (ORCID: https://orcid.org/0000-0002-8565-6011)
- Zhiyou Fang (ORCID: https://orcid.org/0000-0001-5135-7382)
- Xing Liu (ORCID: https://orcid.org/0000-0002-7480-5085)
- Fangyuan Xiong
- Peng Xia (ORCID: https://orcid.org/0000-0001-7448-4464)
- Hao Jiang (ORCID: https://orcid.org/0009-0009-9296-6067)
- Ting Zhang (ORCID: https://orcid.org/0000-0001-5676-4825)
Institutions
- University of Science and Technology of China (CN)
- Sichuan University (CN)
- Hefei Institutes of Physical Science (CN)
- ShanghaiTech University (CN)
- West China Hospital of Sichuan University (CN)
- Hefei National Center for Physical Sciences at Nanoscale (CN)
- Cancer Hospital of Chinese Academy of Medical Sciences (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114739
- Citations
- 6
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.96
Funders
- National Natural Science Foundation of China
- Ministry of Education of the People's Republic of China
- Ministry of Science and Technology of the People's Republic of China