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Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors

Author

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  • Ryuichiro Nakato

    (The University of Tokyo)

  • Toyonori Sakata

    (The University of Tokyo
    Karolinska Institutet, Department of Biosciences and Nutrition, Biomedicum
    Karolinska Institutet, Department of Cell and Molecular Biology, Biomedicum)

  • Jiankang Wang

    (Hunan University)

  • Luis Augusto Eijy Nagai

    (The University of Tokyo)

  • Yuya Nagaoka

    (The University of Tokyo)

  • Gina Miku Oba

    (The University of Tokyo)

  • Masashige Bando

    (The University of Tokyo)

  • Katsuhiko Shirahige

    (The University of Tokyo
    Karolinska Institutet, Department of Biosciences and Nutrition, Biomedicum
    Karolinska Institutet, Department of Cell and Molecular Biology, Biomedicum)

Abstract

Cohesin regulates gene expression through context-specific chromatin folding mechanisms such as enhancer–promoter looping and topologically associating domain (TAD) formation by cooperating with factors such as cohesin loaders and the insulation factor CTCF. We developed a computational workflow to explore how three-dimensional (3D) structure and gene expression are regulated collectively or individually by cohesin and related factors. The main component is CustardPy, by which multi-omics datasets are compared systematically. To validate our methodology, we generated 3D genome, transcriptome, and epigenome data before and after depletion of cohesin and related factors and compared the effects of depletion. We observed diverse effects on the 3D genome and transcriptome, and gene expression changes were correlated with the splitting of TADs caused by cohesin loss. We also observed variations in long-range interactions across TADs, which correlated with their epigenomic states. These computational tools and datasets will be valuable for 3D genome and epigenome studies.

Suggested Citation

  • Ryuichiro Nakato & Toyonori Sakata & Jiankang Wang & Luis Augusto Eijy Nagai & Yuya Nagaoka & Gina Miku Oba & Masashige Bando & Katsuhiko Shirahige, 2023. "Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41316-4
    DOI: 10.1038/s41467-023-41316-4
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    References listed on IDEAS

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