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

Summary: 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 c...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222012834
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author 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_facet 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_sort Rong Zhou
collection DOAJ
description Summary: 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.
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spelling doaj.art-7e8c6a2bad8943179c6a38dd6e1a14f12022-12-22T01:44:23ZengElsevieriScience2589-00422022-09-01259105011CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactionsRong Zhou0Kai Tian1Jie Huang2Wenjia Duan3Hongye Fu4Ying Feng5Hui Wang6Yongpeng Jiang7Yuanjun Li8Rui Wang9Jiazhi Hu10Hanhui Ma11Zhi Qi12Xiong Ji13Key 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaCenter for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaKey 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, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai 201210, ChinaCenter for Quantitative Biology, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Corresponding authorKey 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; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222012834Biological sciencesMolecular biologyMolecular interaction
spellingShingle 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
CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
iScience
Biological sciences
Molecular biology
Molecular interaction
title CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
title_full CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
title_fullStr CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
title_full_unstemmed CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
title_short CTCF DNA-binding domain undergoes dynamic and selective protein–protein interactions
title_sort ctcf dna binding domain undergoes dynamic and selective protein protein interactions
topic Biological sciences
Molecular biology
Molecular interaction
url http://www.sciencedirect.com/science/article/pii/S2589004222012834
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