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Nucleosome plasticity is a critical element of chromatin liquid–liquid phase separation and multivalent nucleosome interactions

Author

Listed:
  • Stephen E. Farr

    (University of Cambridge)

  • Esmae J. Woods

    (University of Cambridge)

  • Jerelle A. Joseph

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Adiran Garaizar

    (University of Cambridge)

  • Rosana Collepardo-Guevara

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

Abstract

Liquid–liquid phase separation (LLPS) is an important mechanism that helps explain the membraneless compartmentalization of the nucleus. Because chromatin compaction and LLPS are collective phenomena, linking their modulation to the physicochemical features of nucleosomes is challenging. Here, we develop an advanced multiscale chromatin model—integrating atomistic representations, a chemically-specific coarse-grained model, and a minimal model—to resolve individual nucleosomes within sub-Mb chromatin domains and phase-separated systems. To overcome the difficulty of sampling chromatin at high resolution, we devise a transferable enhanced-sampling Debye-length replica-exchange molecular dynamics approach. We find that nucleosome thermal fluctuations become significant at physiological salt concentrations and destabilize the 30-nm fiber. Our simulations show that nucleosome breathing favors stochastic folding of chromatin and promotes LLPS by simultaneously boosting the transient nature and heterogeneity of nucleosome–nucleosome contacts, and the effective nucleosome valency. Our work puts forward the intrinsic plasticity of nucleosomes as a key element in the liquid-like behavior of nucleosomes within chromatin, and the regulation of chromatin LLPS.

Suggested Citation

  • Stephen E. Farr & Esmae J. Woods & Jerelle A. Joseph & Adiran Garaizar & Rosana Collepardo-Guevara, 2021. "Nucleosome plasticity is a critical element of chromatin liquid–liquid phase separation and multivalent nucleosome interactions," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23090-3
    DOI: 10.1038/s41467-021-23090-3
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    Cited by:

    1. Khalil Joron & Juliane Oliveira Viegas & Liam Haas-Neill & Sariel Bier & Paz Drori & Shani Dvir & Patrick Siang Lin Lim & Sarah Rauscher & Eran Meshorer & Eitan Lerner, 2023. "Fluorescent protein lifetimes report densities and phases of nuclear condensates during embryonic stem-cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. 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.
    3. Kayo Hibino & Yuji Sakai & Sachiko Tamura & Masatoshi Takagi & Katsuhiko Minami & Toyoaki Natsume & Masa A. Shimazoe & Masato T. Kanemaki & Naoko Imamoto & Kazuhiro Maeshima, 2024. "Single-nucleosome imaging unveils that condensins and nucleosome–nucleosome interactions differentially constrain chromatin to organize mitotic chromosomes," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. 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.

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