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SPIN reveals genome-wide landscape of nuclear compartmentalization

Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric Hupkes, Yu Chen, View ORCID ProfileDavid M. Gilbert, View ORCID ProfileBas van Steensel, View ORCID ProfileAndrew S. Belmont, View ORCID ProfileJian Ma
doi: https://doi.org/10.1101/2020.03.09.982967
Yuchuan Wang
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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Yang Zhang
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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Ruochi Zhang
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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Tom van Schaik
2Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1016 HM, Amsterdam, The Netherlands
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Liguo Zhang
3Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, USA
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Takayo Sasaki
4Department of Biological Science, The Florida State University, Tallahassee, FL 32304, USA
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Daniel Peric Hupkes
2Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1016 HM, Amsterdam, The Netherlands
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Yu Chen
3Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, USA
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David M. Gilbert
4Department of Biological Science, The Florida State University, Tallahassee, FL 32304, USA
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  • ORCID record for David M. Gilbert
Bas van Steensel
2Division of Gene Regulation, Netherlands Cancer Institute, Plesmanlaan 121, 1016 HM, Amsterdam, The Netherlands
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  • ORCID record for Bas van Steensel
Andrew S. Belmont
3Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801, USA
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Jian Ma
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA
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  • ORCID record for Jian Ma
  • For correspondence: jianma@cs.cmu.edu
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Abstract

Chromosomes segregate differentially relative to distinct subnuclear structures, but this genome-wide compartmentalization, pivotal for modulating genome function, remains poorly understood. New genomic mapping methods can reveal chromosome positioning relative to specific nuclear structures. However, computational methods that integrate their results to identify overall intranuclear chromo-some positioning have not yet been developed. We report SPIN, a new method to identify genome-wide nuclear spatial localization patterns. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping (TSA-seq and DamID) and chromatin interaction data (Hi-C) from K562 cells to identify 10 spatial compartmentalization states genome-wide relative to nuclear speckles, lamina, and nucleoli. These SPIN states show novel patterns of genome spatial organization and their relation to genome function (transcription and replication timing). Comparisons of SPIN states with Hi-C sub-compartments and lamina-associated domains (LADs) from multiple cell types suggest constitutive compartmentalization patterns. By integrating different readouts of higher-order genome organization, SPIN provides critical insights into nuclear spatial and functional compartmentalization.

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Posted March 10, 2020.
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SPIN reveals genome-wide landscape of nuclear compartmentalization
Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric Hupkes, Yu Chen, David M. Gilbert, Bas van Steensel, Andrew S. Belmont, Jian Ma
bioRxiv 2020.03.09.982967; doi: https://doi.org/10.1101/2020.03.09.982967
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SPIN reveals genome-wide landscape of nuclear compartmentalization
Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric Hupkes, Yu Chen, David M. Gilbert, Bas van Steensel, Andrew S. Belmont, Jian Ma
bioRxiv 2020.03.09.982967; doi: https://doi.org/10.1101/2020.03.09.982967

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