IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48370-6.html
   My bibliography  Save this article

Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells

Author

Listed:
  • Andrea M. Chiariello

    (Complesso Universitario di Monte Sant’Angelo)

  • Alex Abraham

    (Complesso Universitario di Monte Sant’Angelo)

  • Simona Bianco

    (Complesso Universitario di Monte Sant’Angelo)

  • Andrea Esposito

    (Complesso Universitario di Monte Sant’Angelo)

  • Andrea Fontana

    (Complesso Universitario di Monte Sant’Angelo)

  • Francesca Vercellone

    (Università degli Studi di Napoli Federico II, and INFN Napoli)

  • Mattia Conte

    (Complesso Universitario di Monte Sant’Angelo)

  • Mario Nicodemi

    (Complesso Universitario di Monte Sant’Angelo
    Berlin Institute for Medical Systems Biology at the Max Delbruck Center for Molecular Medicine in the Helmholtz Association)

Abstract

SARS-CoV-2 can re-structure chromatin organization and alter the epigenomic landscape of the host genome, but the mechanisms that produce such changes remain unclear. Here, we use polymer physics to investigate how the chromatin of the host genome is re-organized upon infection with SARS-CoV-2. We show that re-structuring of A/B compartments can be explained by a re-modulation of intra-compartment homo-typic affinities, which leads to the weakening of A-A interactions and the enhancement of A-B mixing. At the TAD level, re-arrangements are physically described by a reduction in the loop extrusion activity coupled with an alteration of chromatin phase-separation properties, resulting in more intermingling between different TADs and a spread in space of the TADs themselves. In addition, the architecture of loci relevant to the antiviral interferon response, such as DDX58 or IFIT, becomes more variable within the 3D single-molecule population of the infected model, suggesting that viral infection leads to a loss of chromatin structural specificity. Analysing the time trajectories of pairwise gene-enhancer and higher-order contacts reveals that this variability derives from increased fluctuations in the chromatin dynamics of infected cells. This suggests that SARS-CoV-2 alters gene regulation by impacting the stability of the contact network in time.

Suggested Citation

  • Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Andrea Fontana & Francesca Vercellone & Mattia Conte & Mario Nicodemi, 2024. "Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48370-6
    DOI: 10.1038/s41467-024-48370-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48370-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-48370-6?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. Mattia Conte & Luca Fiorillo & Simona Bianco & Andrea M. Chiariello & Andrea Esposito & Mario Nicodemi, 2020. "Polymer physics indicates chromatin folding variability across single-cells results from state degeneracy in phase separation," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    2. David E. Gordon & Gwendolyn M. Jang & Mehdi Bouhaddou & Jiewei Xu & Kirsten Obernier & Kris M. White & Matthew J. O’Meara & Veronica V. Rezelj & Jeffrey Z. Guo & Danielle L. Swaney & Tia A. Tummino & , 2020. "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing," Nature, Nature, vol. 583(7816), pages 459-468, July.
    3. Martin Falk & Yana Feodorova & Natalia Naumova & Maxim Imakaev & Bryan R. Lajoie & Heinrich Leonhardt & Boris Joffe & Job Dekker & Geoffrey Fudenberg & Irina Solovei & Leonid A. Mirny, 2019. "Publisher Correction: Heterochromatin drives compartmentalization of inverted and conventional nuclei," Nature, Nature, vol. 572(7771), pages 22-22, August.
    4. Wibke Schwarzer & Nezar Abdennur & Anton Goloborodko & Aleksandra Pekowska & Geoffrey Fudenberg & Yann Loe-Mie & Nuno A Fonseca & Wolfgang Huber & Christian H. Haering & Leonid Mirny & Francois Spitz, 2017. "Two independent modes of chromatin organization revealed by cohesin removal," Nature, Nature, vol. 551(7678), pages 51-56, November.
    5. Job Dekker & Andrew S. Belmont & Mitchell Guttman & Victor O. Leshyk & John T. Lis & Stavros Lomvardas & Leonid A. Mirny & Clodagh C. O’Shea & Peter J. Park & Bing Ren & Joan C. Ritland Politz & Jay S, 2017. "Correction: Corrigendum: The 4D nucleome project," Nature, Nature, vol. 552(7684), pages 278-278, December.
    6. Martin Falk & Yana Feodorova & Natalia Naumova & Maxim Imakaev & Bryan R. Lajoie & Heinrich Leonhardt & Boris Joffe & Job Dekker & Geoffrey Fudenberg & Irina Solovei & Leonid A. Mirny, 2019. "Heterochromatin drives compartmentalization of inverted and conventional nuclei," Nature, Nature, vol. 570(7761), pages 395-399, June.
    7. Job Dekker & Andrew S. Belmont & Mitchell Guttman & Victor O. Leshyk & John T. Lis & Stavros Lomvardas & Leonid A. Mirny & Clodagh C. O’Shea & Peter J. Park & Bing Ren & Joan C. Ritland Politz & Jay S, 2017. "The 4D nucleome project," Nature, Nature, vol. 549(7671), pages 219-226, September.
    8. Guang Shi & Lei Liu & Changbong Hyeon & D. Thirumalai, 2018. "Interphase human chromosome exhibits out of equilibrium glassy dynamics," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    9. Mattia Conte & Ehsan Irani & Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Mario Nicodemi, 2022. "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    10. John Kee & Samuel Thudium & David M. Renner & Karl Glastad & Katherine Palozola & Zhen Zhang & Yize Li & Yemin Lan & Joseph Cesare & Andrey Poleshko & Anna A. Kiseleva & Rachel Truitt & Fabian L. Card, 2022. "SARS-CoV-2 disrupts host epigenetic regulation via histone mimicry," Nature, Nature, vol. 610(7931), pages 381-388, October.
    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. Sangram Kadam & Kiran Kumari & Vinoth Manivannan & Shuvadip Dutta & Mithun K. Mitra & Ranjith Padinhateeri, 2023. "Predicting scale-dependent chromatin polymer properties from systematic coarse-graining," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    4. Mattia Conte & Ehsan Irani & Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Mario Nicodemi, 2022. "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    6. Ting Peng & Yingping Hou & Haowei Meng & Yong Cao & Xiaotian Wang & Lumeng Jia & Qing Chen & Yang Zheng & Yujie Sun & Hebing Chen & Tingting Li & Cheng Li, 2023. "Mapping nucleolus-associated chromatin interactions using nucleolus Hi-C reveals pattern of heterochromatin interactions," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Jorine M. Eeftens & Manya Kapoor & Davide Michieletto & Clifford P. Brangwynne, 2021. "Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    8. Manisha Poudyal & Komal Patel & Laxmikant Gadhe & Ajay Singh Sawner & Pradeep Kadu & Debalina Datta & Semanti Mukherjee & Soumik Ray & Ambuja Navalkar & Siddhartha Maiti & Debdeep Chatterjee & Jyoti D, 2023. "Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    9. 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.
    10. Abhijit Chakraborty & Jeffrey G. Wang & Ferhat Ay, 2022. "dcHiC detects differential compartments across multiple Hi-C datasets," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    11. Mayank N. K. Choudhary & Kara Quaid & Xiaoyun Xing & Heather Schmidt & Ting Wang, 2023. "Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Jingxuan Xu & Xiang Xu & Dandan Huang & Yawen Luo & Lin Lin & Xuemei Bai & Yang Zheng & Qian Yang & Yu Cheng & An Huang & Jingyi Shi & Xiaochen Bo & Jin Gu & Hebing Chen, 2024. "A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    13. Haowen Zhang & Li Song & Xiaotao Wang & Haoyu Cheng & Chenfei Wang & Clifford A. Meyer & Tao Liu & Ming Tang & Srinivas Aluru & Feng Yue & X. Shirley Liu & Heng Li, 2021. "Fast alignment and preprocessing of chromatin profiles with Chromap," Nature Communications, Nature, vol. 12(1), pages 1-6, December.
    14. Hao Wang & Jiaxin Yang & Yu Zhang & Jianliang Qian & Jianrong Wang, 2022. "Reconstruct high-resolution 3D genome structures for diverse cell-types using FLAMINGO," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. Zhongxuan Zhang & Xiaoxiao Rong & Tianjin Xie & Zehao Li & Haozhi Song & Shujun Zhen & Haifeng Wang & Jiahui Wu & Samie R. Jaffrey & Xing Li, 2024. "Fluorogenic CRISPR for genomic DNA imaging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    16. Riccardo Calandrelli & Xingzhao Wen & John Lalith Charles Richard & Zhifei Luo & Tri C. Nguyen & Chien-Ju Chen & Zhijie Qi & Shuanghong Xue & Weizhong Chen & Zhangming Yan & Weixin Wu & Kathia Zaleta-, 2023. "Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Hannah L. Harris & Huiya Gu & Moshe Olshansky & Ailun Wang & Irene Farabella & Yossi Eliaz & Achyuth Kalluchi & Akshay Krishna & Mozes Jacobs & Gesine Cauer & Melanie Pham & Suhas S. P. Rao & Olga Dud, 2023. "Chromatin alternates between A and B compartments at kilobase scale for subgenic organization," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    18. Tengfei Wang & Shuxiang Shi & Yuanyuan Shi & Peipei Jiang & Ganlu Hu & Qinying Ye & Zhan Shi & Kexin Yu & Chenguang Wang & Guoping Fan & Suwen Zhao & Hanhui Ma & Alex C. Y. Chang & Zhi Li & Qian Bian , 2023. "Chemical-induced phase transition and global conformational reorganization of chromatin," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    19. Markus Götz & Olivier Messina & Sergio Espinola & Jean-Bernard Fiche & Marcelo Nollmann, 2022. "Multiple parameters shape the 3D chromatin structure of single nuclei at the doc locus in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Sarah B. Reiff & Andrew J. Schroeder & Koray Kırlı & Andrea Cosolo & Clara Bakker & Luisa Mercado & Soohyun Lee & Alexander D. Veit & Alexander K. Balashov & Carl Vitzthum & William Ronchetti & Kent M, 2022. "The 4D Nucleome Data Portal as a resource for searching and visualizing curated nucleomics data," Nature Communications, Nature, vol. 13(1), pages 1-11, 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:15:y:2024:i:1:d:10.1038_s41467-024-48370-6. 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.