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Sep 16, 2022;25 (9): 105011.

CTCF DNA-binding domain undergoes dynamic and selective protein-protein interactions.

Rong Zhou, Kai Tian, Jie Huang, Wenjia Duan, Hongye Fu, Ying Feng, Hui Wang, Yongpeng Jiang, Yuanjun Li, Rui Wang, Jiazhi Hu, Hanhui Ma, Zhi Qi, Xiong Ji
Author Information
  1. Rong Zhou: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  2. Kai Tian: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  3. Jie Huang: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  4. Wenjia Duan: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  5. Hongye Fu: Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  6. Ying Feng: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  7. Hui Wang: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  8. Yongpeng Jiang: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  9. Yuanjun Li: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  10. Rui Wang: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  11. Jiazhi Hu: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
  12. Hanhui Ma: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  13. Zhi Qi: Center for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  14. Xiong Ji: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
PMID: 36117989 DOI: 10.1016/j.isci.2022.105011

Abstract

CTCF is a predominant insulator protein required for three-dimensional chromatin organization. However, the roles of its insulation of enhancers in a 3D nuclear organization have not been fully explained. Here, we found that the CTCF DNA-binding domain (DBD) forms dynamic self-interacting clusters. Strikingly, CTCF DBD clusters were found to incorporate other insulator proteins but are not coenriched with transcriptional activators in the nucleus. This property is not observed in other domains of CTCF or the DBDs of other transcription factors. Moreover, endogenous CTCF shows a phenotype consistent with the DBD by forming small protein clusters and interacting with CTCF motif arrays that have fewer transcriptional activators bound. Our results reveal an interesting phenomenon in which CTCF DBD interacts with insulator proteins and selectively localizes to nuclear positions with lower concentrations of transcriptional activators, providing insights into the insulation function of CTCF.

Keywords

Biological sciences Molecular biology Molecular interaction

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