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The structural basis for cohesin–CTCF-anchored loops

Author

Listed:
  • Yan Li

    (European Molecular Biology Laboratory)

  • Judith H. I. Haarhuis

    (The Netherlands Cancer Institute)

  • Ángela Sedeño Cacciatore

    (The Netherlands Cancer Institute)

  • Roel Oldenkamp

    (The Netherlands Cancer Institute)

  • Marjon S. Ruiten

    (The Netherlands Cancer Institute)

  • Laureen Willems

    (The Netherlands Cancer Institute)

  • Hans Teunissen

    (The Netherlands Cancer Institute)

  • Kyle W. Muir

    (European Molecular Biology Laboratory
    MRC Laboratory of Molecular Biology)

  • Elzo Wit

    (The Netherlands Cancer Institute)

  • Benjamin D. Rowland

    (The Netherlands Cancer Institute)

  • Daniel Panne

    (European Molecular Biology Laboratory
    University of Leicester)

Abstract

Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2–SCC1 subunits of human cohesin. We report a crystal structure of SA2–SCC1 in complex with CTCF at a resolution of 2.7 Å, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF.

Suggested Citation

  • Yan Li & Judith H. I. Haarhuis & Ángela Sedeño Cacciatore & Roel Oldenkamp & Marjon S. Ruiten & Laureen Willems & Hans Teunissen & Kyle W. Muir & Elzo Wit & Benjamin D. Rowland & Daniel Panne, 2020. "The structural basis for cohesin–CTCF-anchored loops," Nature, Nature, vol. 578(7795), pages 472-476, February.
    • Handle: RePEc:nat:nature:v:578:y:2020:i:7795:d:10.1038_s41586-019-1910-z
    DOI: 10.1038/s41586-019-1910-z
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    Citations

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    Cited by:

    1. Ayantika Sen Gupta & Chris Seidel & Dai Tsuchiya & Sean McKinney & Zulin Yu & Sarah E. Smith & Jay R. Unruh & Jennifer L. Gerton, 2023. "Defining a core configuration for human centromeres during mitosis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Jie Zhang & Gongcheng Hu & Yuli Lu & Huawei Ren & Yin Huang & Yulin Wen & Binrui Ji & Diyang Wang & Haidong Wang & Huisheng Liu & Ning Ma & Lingling Zhang & Guangjin Pan & Yibo Qu & Hua Wang & Wei Zha, 2024. "CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Jin H. Yang & Hugo B. Brandão & Anders S. Hansen, 2023. "DNA double-strand break end synapsis by DNA loop extrusion," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Louisa Hill & Gordana Wutz & Markus Jaritz & Hiromi Tagoh & Lesly Calderón & Jan-Michael Peters & Anton Goloborodko & Meinrad Busslinger, 2023. "Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Ignacio Prusén Mota & Marta Galova & Alexander Schleiffer & Tan-Trung Nguyen & Ines Kovacikova & Carolina Farias Saad & Gabriele Litos & Tomoko Nishiyama & Juraj Gregan & Jan-Michael Peters & Peter Sc, 2024. "Sororin is an evolutionary conserved antagonist of WAPL," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    6. Hye Ji Cha & Özgün Uyan & Yan Kai & Tianxin Liu & Qian Zhu & Zuzana Tothova & Giovanni A. Botten & Jian Xu & Guo-Cheng Yuan & Job Dekker & Stuart H. Orkin, 2021. "Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    7. Li-Hsin Chang & Sourav Ghosh & Andrea Papale & Jennifer M. Luppino & Mélanie Miranda & Vincent Piras & Jéril Degrouard & Joanne Edouard & Mallory Poncelet & Nathan Lecouvreur & Sébastien Bloyer & Amél, 2023. "Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Dácil Alonso-Gil & Ana Cuadrado & Daniel Giménez-Llorente & Miriam Rodríguez-Corsino & Ana Losada, 2023. "Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Shuai Liu & Yaqiang Cao & Kairong Cui & Qingsong Tang & Keji Zhao, 2022. "Hi-TrAC reveals division of labor of transcription factors in organizing chromatin loops," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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