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L1 and B1 repeats blueprint the spatial organization of chromatin

J. Yuyang Lu, Lei Chang, Tong Li, Ting Wang, Yafei Yin, Ge Zhan, Ke Zhang, Michelle Percharde, Liang Wang, Qi Peng, Pixi Yan, Hui Zhang, Xue Han, Xianju Bi, Wen Shao, Yantao Hong, Zhongyang Wu, Peizhe Wang, Wenzhi Li, Jing Zhang, Zai Chang, Yingping Hou, Pilong Li, Miguel Ramalho-Santos, Jie Na, Wei Xie, Yujie Sun, View ORCID ProfileXiaohua Shen
doi: https://doi.org/10.1101/802173
J. Yuyang Lu
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Lei Chang
2State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China
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Tong Li
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Ting Wang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Yafei Yin
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Ge Zhan
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Ke Zhang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Michelle Percharde
4MRC LMS & Imperial College London, London W12 0NN, UK
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Liang Wang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Qi Peng
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Pixi Yan
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Hui Zhang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Xue Han
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Xianju Bi
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Wen Shao
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Yantao Hong
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Zhongyang Wu
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Peizhe Wang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Wenzhi Li
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Jing Zhang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Zai Chang
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Yingping Hou
2State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China
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Pilong Li
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Miguel Ramalho-Santos
5Lunenfeld-Tanenbaum Research Institute, University of Toronto, Ontario M5T 3H7, Canada
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Jie Na
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Wei Xie
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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Yujie Sun
2State Key Laboratory of Membrane Biology, School of Life Sciences, and Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China
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  • For correspondence: xshen@tsinghua.edu.cn sun_yujie@pku.edu.cn
Xiaohua Shen
1Tsinghua Center for Life Sciences, School of Medicine and School of Life Scikences, Tsinghua University, Beijing 100084, China
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  • ORCID record for Xiaohua Shen
  • For correspondence: xshen@tsinghua.edu.cn sun_yujie@pku.edu.cn
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SUMMARY

Despite extensive mapping of three-dimensional (3D) chromatin structures, the basic principles underlying genome folding remain unknown. Here, we report a fundamental role for L1 and B1 retrotransposons in shaping the macroscopic 3D genome structure. Homotypic clustering of B1 and L1 repeats in the nuclear interior or at the nuclear and nucleolar peripheries, respectively, segregates the genome into mutually exclusive nuclear compartments. This spatial segregation of L1 and B1 is conserved in mouse and human cells, and occurs dynamically during establishment of the 3D chromatin structure in early embryogenesis and the cell cycle. Depletion of L1 transcripts drastically disrupts the spatial distributions of L1- and B1-rich compartments. L1 transcripts are strongly associated with L1 DNA sequences and induce phase separation of the heterochromatin protein HP1α. Our results suggest that genomic repeats act as the blueprint of chromatin macrostructure, thus explaining the conserved higher-order structure of chromatin across mammalian cells.

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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 October 13, 2019.
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L1 and B1 repeats blueprint the spatial organization of chromatin
J. Yuyang Lu, Lei Chang, Tong Li, Ting Wang, Yafei Yin, Ge Zhan, Ke Zhang, Michelle Percharde, Liang Wang, Qi Peng, Pixi Yan, Hui Zhang, Xue Han, Xianju Bi, Wen Shao, Yantao Hong, Zhongyang Wu, Peizhe Wang, Wenzhi Li, Jing Zhang, Zai Chang, Yingping Hou, Pilong Li, Miguel Ramalho-Santos, Jie Na, Wei Xie, Yujie Sun, Xiaohua Shen
bioRxiv 802173; doi: https://doi.org/10.1101/802173
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L1 and B1 repeats blueprint the spatial organization of chromatin
J. Yuyang Lu, Lei Chang, Tong Li, Ting Wang, Yafei Yin, Ge Zhan, Ke Zhang, Michelle Percharde, Liang Wang, Qi Peng, Pixi Yan, Hui Zhang, Xue Han, Xianju Bi, Wen Shao, Yantao Hong, Zhongyang Wu, Peizhe Wang, Wenzhi Li, Jing Zhang, Zai Chang, Yingping Hou, Pilong Li, Miguel Ramalho-Santos, Jie Na, Wei Xie, Yujie Sun, Xiaohua Shen
bioRxiv 802173; doi: https://doi.org/10.1101/802173

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