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A self-blinking DNA probe for live-cell superresolution 3D imaging of hierarchical chromatin structures

View ORCID ProfileYang Zheng, View ORCID ProfileSen Ye, View ORCID ProfileShumin Li, Cuifang Liu, Shihang Luo, Yanqin Chen, Yunsheng Li, Lingyi Huang, Shan Deng, Ping Chen, Yongdeng Zhang, Wei Ji, View ORCID ProfileRuibang Luo, Guohong Li, Dan Yang
doi: https://doi.org/10.1101/2022.06.22.497271
Yang Zheng
1Morningside Laboratory for Chemical Biology and Department of Chemistry, The University of Hong Kong, Hong Kong, China
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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  • ORCID record for Yang Zheng
Sen Ye
1Morningside Laboratory for Chemical Biology and Department of Chemistry, The University of Hong Kong, Hong Kong, China
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  • ORCID record for Sen Ye
Shumin Li
3Department of Computer Science, The University of Hong Kong, Hong Kong, China
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Cuifang Liu
4National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
5College of Life Science, University of Chinese Academy of Sciences, Beijing, China
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Shihang Luo
5College of Life Science, University of Chinese Academy of Sciences, Beijing, China
7Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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Yanqin Chen
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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Yunsheng Li
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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Lingyi Huang
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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Shan Deng
1Morningside Laboratory for Chemical Biology and Department of Chemistry, The University of Hong Kong, Hong Kong, China
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Ping Chen
4National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
8Department of Immunology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
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Yongdeng Zhang
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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Wei Ji
5College of Life Science, University of Chinese Academy of Sciences, Beijing, China
7Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
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Ruibang Luo
3Department of Computer Science, The University of Hong Kong, Hong Kong, China
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Guohong Li
4National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
5College of Life Science, University of Chinese Academy of Sciences, Beijing, China
6Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong, China
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  • For correspondence: liguohong@ibp.ac.cn yangdan@westlake.edu.cn
Dan Yang
1Morningside Laboratory for Chemical Biology and Department of Chemistry, The University of Hong Kong, Hong Kong, China
2School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
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  • For correspondence: liguohong@ibp.ac.cn yangdan@westlake.edu.cn
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ABSTRACT

How the 2-m-long genomic DNA is packaged into chromatin in the 10-µm eukaryotic nucleus is a fundamental question in cell biology. DNA accessibility depends on chromatin structure and dynamics, which basically control all DNA-related processes, such as transcription, DNA replication and repair. The hierarchical model of chromatin organization has been controversial in recent years because live-cell evidence for the existence of chromatin fibers, particularly those 30 nm in diameter, has remained elusive. Herein, we report a DNA-binding, fluorogenic and self-blinking small-molecule probe for the first live-cell 3D superresolution imaging of chromatin fibers with structural plasticity and fast dynamics. Selective inhibition of histone deacetylases led to decompaction of chromatin fibers due to hyperacetylation of histones. Our live-cell imaging results suggest a model of DNA packaging in interphase with the hierarchical organization of nucleosomal arrays and chromatin fibers.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Title slighly modified. Abstract and introduction revised. Fig. 5 revised.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 24, 2022.
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A self-blinking DNA probe for live-cell superresolution 3D imaging of hierarchical chromatin structures
Yang Zheng, Sen Ye, Shumin Li, Cuifang Liu, Shihang Luo, Yanqin Chen, Yunsheng Li, Lingyi Huang, Shan Deng, Ping Chen, Yongdeng Zhang, Wei Ji, Ruibang Luo, Guohong Li, Dan Yang
bioRxiv 2022.06.22.497271; doi: https://doi.org/10.1101/2022.06.22.497271
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A self-blinking DNA probe for live-cell superresolution 3D imaging of hierarchical chromatin structures
Yang Zheng, Sen Ye, Shumin Li, Cuifang Liu, Shihang Luo, Yanqin Chen, Yunsheng Li, Lingyi Huang, Shan Deng, Ping Chen, Yongdeng Zhang, Wei Ji, Ruibang Luo, Guohong Li, Dan Yang
bioRxiv 2022.06.22.497271; doi: https://doi.org/10.1101/2022.06.22.497271

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