IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-57775-w.html
   My bibliography  Save this article

High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion

Author

Listed:
  • Corriene E. Sept

    (Harvard T.H. Chan School of Public Health
    Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Y. Esther Tak

    (Massachusetts General Hospital
    Harvard Medical School)

  • Viraat Goel

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Koch Institute for Integrative Cancer Research
    Broad Institute of MIT and Harvard)

  • Mital S. Bhakta

    (Cantata Bio LLC)

  • Christian G. Cerda-Smith

    (Duke University School of Medicine)

  • Haley M. Hutchinson

    (Duke University School of Medicine)

  • Marco Blanchette

    (Liftoff Biosolution)

  • Christine E. Eyler

    (Duke University School of Medicine
    Duke University School of Medicine)

  • Sarah E. Johnstone

    (Broad Institute of MIT and Harvard
    Dana-Farber Cancer Institute)

  • J. Keith Joung

    (Massachusetts General Hospital
    Harvard Medical School)

  • Anders S. Hansen

    (Broad Institute of MIT and Harvard
    Massachusetts Institute of Technology
    Koch Institute for Integrative Cancer Research
    Broad Institute of MIT and Harvard)

  • Martin J. Aryee

    (Harvard T.H. Chan School of Public Health
    Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard
    Arena Bioworks)

Abstract

Cohesin-mediated DNA loop extrusion enables gene regulation by distal enhancers through the establishment of chromosome structure and long-range enhancer-promoter interactions. The best characterized cohesin-related structures, such as topologically associating domains (TADs) anchored at convergent CTCF binding sites, represent static conformations. Consequently, loop extrusion dynamics remain poorly understood. To better characterize static and dynamically extruding chromatin loop structures, we use MNase-based 3D genome assays to simultaneously determine CTCF and cohesin localization as well as the 3D contacts they mediate. Here we present CTCF Analyzer (with) Multinomial Estimation (CAMEL), a tool that identifies CTCF footprints at near base-pair resolution in CTCF MNase HiChiP. We also use Region Capture Micro-C to identify a CTCF-adjacent footprint that is attributed to cohesin occupancy. We leverage this substantial advance in resolution to determine that the fully extruded (CTCF-CTCF loop) state is rare genome-wide with locus-specific variation from ~1–10%. We further investigate the impact of chromatin state on loop extrusion dynamics and find that active regulatory elements impede cohesin extrusion. These findings support a model of topological regulation whereby the transient, partially extruded state facilitates enhancer-promoter contacts that can regulate transcription.

Suggested Citation

  • Corriene E. Sept & Y. Esther Tak & Viraat Goel & Mital S. Bhakta & Christian G. Cerda-Smith & Haley M. Hutchinson & Marco Blanchette & Christine E. Eyler & Sarah E. Johnstone & J. Keith Joung & Anders, 2025. "High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57775-w
    DOI: 10.1038/s41467-025-57775-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-57775-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-57775-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Georg A. Busslinger & Roman R. Stocsits & Petra van der Lelij & Elin Axelsson & Antonio Tedeschi & Niels Galjart & Jan-Michael Peters, 2017. "Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl," Nature, Nature, vol. 544(7651), pages 503-507, April.
    2. Armelle Lengronne & Yuki Katou & Saori Mori & Shihori Yokobayashi & Gavin P. Kelly & Takehiko Itoh & Yoshinori Watanabe & Katsuhiko Shirahige & Frank Uhlmann, 2004. "Cohesin relocation from sites of chromosomal loading to places of convergent transcription," Nature, Nature, vol. 430(6999), pages 573-578, July.
    3. Fionn Murtagh & Pierre Legendre, 2014. "Ward’s Hierarchical Agglomerative Clustering Method: Which Algorithms Implement Ward’s Criterion?," Journal of Classification, Springer;The Classification Society, vol. 31(3), pages 274-295, October.
    4. 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.
    5. Lanbo Xiao & Abhijit Parolia & Yuanyuan Qiao & Pushpinder Bawa & Sanjana Eyunni & Rahul Mannan & Sandra E. Carson & Yu Chang & Xiaoju Wang & Yuping Zhang & Josh N. Vo & Steven Kregel & Stephanie A. Si, 2022. "Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer," Nature, Nature, vol. 601(7893), pages 434-439, January.
    6. Sourya Bhattacharyya & Vivek Chandra & Pandurangan Vijayanand & Ferhat Ay, 2019. "Identification of significant chromatin contacts from HiChIP data by FitHiChIP," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    7. Elphège P. Nora & Laura Caccianini & Geoffrey Fudenberg & Kevin So & Vasumathi Kameswaran & Abigail Nagle & Alec Uebersohn & Bassam Hajj & Agnès Le Saux & Antoine Coulon & Leonid A. Mirny & Katherine , 2020. "Molecular basis of CTCF binding polarity in genome folding," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    8. William A. Flavahan & Yotam Drier & Brian B. Liau & Shawn M. Gillespie & Andrew S. Venteicher & Anat O. Stemmer-Rachamimov & Mario L. Suvà & Bradley E. Bernstein, 2016. "Insulator dysfunction and oncogene activation in IDH mutant gliomas," Nature, Nature, vol. 529(7584), pages 110-114, January.
    9. Soohwan Oh & Jiaofang Shao & Joydeep Mitra & Feng Xiong & Matteo D’Antonio & Ruoyu Wang & Ivan Garcia-Bassets & Qi Ma & Xiaoyu Zhu & Joo-Hyung Lee & Sreejith J. Nair & Feng Yang & Kenneth Ohgi & Kelly, 2021. "Enhancer release and retargeting activates disease-susceptibility genes," Nature, Nature, vol. 595(7869), pages 735-740, July.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Evelyn Kabirova & Anastasiya Ryzhkova & Varvara Lukyanchikova & Anna Khabarova & Alexey Korablev & Tatyana Shnaider & Miroslav Nuriddinov & Polina Belokopytova & Alexander Smirnov & Nikita V. Khotskin, 2024. "TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Jonas Coßmann & Pavel I. Kos & Vassiliki Varamogianni-Mamatsi & Devin S. Assenheimer & Tobias A. Bischof & Timo Kuhn & Thomas Vomhof & Argyris Papantonis & Luca Giorgetti & J. Christof M. Gebhardt, 2025. "Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    3. 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.
    4. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. 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.
    6. 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.
    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. Jia-Yong Zhong & Longjian Niu & Zhuo-Bin Lin & Xin Bai & Ying Chen & Feng Luo & Chunhui Hou & Chuan-Le Xiao, 2023. "High-throughput Pore-C reveals the single-allele topology and cell type-specificity of 3D genome folding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Aayush Kant & Zixian Guo & Vinayak Vinayak & Maria Victoria Neguembor & Wing Shun Li & Vasundhara Agrawal & Emily Pujadas & Luay Almassalha & Vadim Backman & Melike Lakadamyali & Maria Pia Cosma & Viv, 2024. "Active transcription and epigenetic reactions synergistically regulate meso-scale genomic organization," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Silvia Peripolli & Leticia Meneguello & Chiara Perrod & Tanya Singh & Harshil Patel & Sazia T. Rahman & Koshiro Kiso & Peter Thorpe & Vincenzo Calvanese & Cosetta Bertoli & Robertus A. M. de Bruin, 2024. "Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    11. 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.
    12. 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.
    13. Maurizio Vichi & Carlo Cavicchia & Patrick J. F. Groenen, 2022. "Hierarchical Means Clustering," Journal of Classification, Springer;The Classification Society, vol. 39(3), pages 553-577, November.
    14. Jiao Jieying & Hu Guanyu & Yan Jun, 2021. "A Bayesian marked spatial point processes model for basketball shot chart," Journal of Quantitative Analysis in Sports, De Gruyter, vol. 17(2), pages 77-90, June.
    15. Paulus, Michal & Kristoufek, Ladislav, 2015. "Worldwide clustering of the corruption perception," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 428(C), pages 351-358.
    16. Hyeri Choi & Min Jae Park, 2019. "Evaluating the Efficiency of Governmental Excellence for Social Progress: Focusing on Low- and Lower-Middle-Income Countries," Social Indicators Research: An International and Interdisciplinary Journal for Quality-of-Life Measurement, Springer, vol. 141(1), pages 111-130, January.
    17. Maksym Polyakov & Morteza Chalak & Md. Sayed Iftekhar & Ram Pandit & Sorada Tapsuwan & Fan Zhang & Chunbo Ma, 2018. "Authorship, Collaboration, Topics, and Research Gaps in Environmental and Resource Economics 1991–2015," Environmental & Resource Economics, Springer;European Association of Environmental and Resource Economists, vol. 71(1), pages 217-239, September.
    18. repec:ers:journl:v:xxiv:y:2021:i:3:p:934-948 is not listed on IDEAS
    19. Giger, Markus & Mutea, Emily & Kiteme, Boniface & Eckert, Sandra & Anseeuw, Ward & Zaehringer, Julie G., 2020. "Large agricultural investments in Kenya’s Nanyuki Area: Inventory and analysis of business models," Land Use Policy, Elsevier, vol. 99(C).
    20. Walker, Nathan L. & Styles, David & Coughlan, Paul & Williams, A. Prysor, 2022. "Cross-sector sustainability benchmarking of major utilities in the United Kingdom," Utilities Policy, Elsevier, vol. 78(C).
    21. Pierre H. H. Schneeberger & Morgan Gueuning & Sophie Welsche & Eveline Hürlimann & Julian Dommann & Cécile Häberli & Jürg E. Frey & Somphou Sayasone & Jennifer Keiser, 2022. "Different gut microbial communities correlate with efficacy of albendazole-ivermectin against soil-transmitted helminthiases," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57775-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.