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From 1D sequence to 3D chromatin dynamics and cellular functions: a phase separation perspective

Sirui Liu, Ling Zhang, Hui Quan, Hao Tian, Luming Meng, Lijiang Yang, Huajie Feng, Yi Qin Gao
doi: https://doi.org/10.1101/255174
Sirui Liu
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Ling Zhang
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
2Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
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Hui Quan
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Hao Tian
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Luming Meng
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Lijiang Yang
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
2Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
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Huajie Feng
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
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Yi Qin Gao
1Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
2Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China.
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  • For correspondence: gaoyq@pku.edu.cn
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Abstract

The high-order chromatin structure plays a non-negligible role in gene regulation. However, the mechanism for the formation of different chromatin structures in different cells and the sequence dependence of this process remain to be elucidated. As the nucleotide distributions in human and mouse genomes are highly uneven, we identified CGI forest and prairie genomic domains based on CGI density, which better segregates genomic elements along the genome than GC content. The genome is then divided into two sequentially, epigenetically, and transcriptionally distinct regions. These two types of megabase-sized domains spatially segregate, but to a different extent in different cell types. Overall, the forests and prairies gradually segregate from each other in development, differentiation, and senescence. The multi-scale forest-prairie spatial intermingling is cell-type specific and increases in differentiation, thus helps define the cell identity. We propose that the phase separation of the 1D mosaic sequence in space, serving as a potential driving force, together with cell type specific epigenetic marks and transcription factors, shapes the chromatin structure in different cell types and renders them distinct genomic properties. The mosaicity of the genome manifested in terms of alternative forests and prairies of a species could be related to its biological processes such as differentiation, aging and body temperature control.

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Posted January 28, 2018.
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From 1D sequence to 3D chromatin dynamics and cellular functions: a phase separation perspective
Sirui Liu, Ling Zhang, Hui Quan, Hao Tian, Luming Meng, Lijiang Yang, Huajie Feng, Yi Qin Gao
bioRxiv 255174; doi: https://doi.org/10.1101/255174
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From 1D sequence to 3D chromatin dynamics and cellular functions: a phase separation perspective
Sirui Liu, Ling Zhang, Hui Quan, Hao Tian, Luming Meng, Lijiang Yang, Huajie Feng, Yi Qin Gao
bioRxiv 255174; doi: https://doi.org/10.1101/255174

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