Dynamic phosphorylation of FOXA1 by Aurora B guides post-mitotic gene reactivation
Ting Zhang,
Shuaiyu Liu,
Olanrewaju Durojaye,
Fangyuan Xiong,
Zhiyou Fang,
Tahir Ullah,
Chuanhai Fu,
Bo Sun,
Hao Jiang,
Peng Xia,
Zhikai Wang,
Xuebiao Yao,
Xing Liu
Affiliations
Ting Zhang
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China
Shuaiyu Liu
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China
Olanrewaju Durojaye
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China
Fangyuan Xiong
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230027, China
Zhiyou Fang
Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei 230027, China
Tahir Ullah
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China
Chuanhai Fu
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China
Bo Sun
School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China
Hao Jiang
West China Hospital, Sichuan University, Chengdu 610041, China
Peng Xia
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Institute of Life Sciences, Zhejiang University, Hangzhou 310058, China
Zhikai Wang
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China; Corresponding author
Xuebiao Yao
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China; Corresponding author
Xing Liu
MOE Key Laboratory for Cellular Dynamics, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Hefei National Research Center for Interdisciplinary Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China; Corresponding author
Summary: 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.
