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

Ryuichiro Nakato (), Toyonori Sakata, Jiankang Wang, Luis Augusto Eijy Nagai, Yuya Nagaoka, Gina Miku Oba, Masashige Bando and Katsuhiko Shirahige ()
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Ryuichiro Nakato: The University of Tokyo
Toyonori Sakata: The University of Tokyo
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

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41316-4

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