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HP1 reshapes nucleosome core to promote phase separation of heterochromatin

Author

Listed:
  • S. Sanulli

    (University of California San Francisco)

  • M. J. Trnka

    (University of California San Francisco)

  • V. Dharmarajan

    (The Scripps Research Institute)

  • R. W. Tibble

    (University of California San Francisco
    University of California San Francisco)

  • B. D. Pascal

    (The Scripps Research Institute)

  • A. L. Burlingame

    (University of California San Francisco)

  • P. R. Griffin

    (The Scripps Research Institute)

  • J. D. Gross

    (University of California San Francisco)

  • G. J. Narlikar

    (University of California San Francisco)

Abstract

Heterochromatin affects genome function at many levels. It enables heritable gene repression, maintains chromosome integrity and provides mechanical rigidity to the nucleus1,2. These diverse functions are proposed to arise in part from compaction of the underlying chromatin2. A major type of heterochromatin contains at its core the complex formed between HP1 proteins and chromatin that is methylated on histone H3, lysine 9 (H3K9me). HP1 is proposed to use oligomerization to compact chromatin into phase-separated condensates3–6. Yet, how HP1-mediated phase separation relates to chromatin compaction remains unclear. Here we show that chromatin compaction by the Schizosaccharomyces pombe HP1 protein Swi6 results in phase-separated liquid condensates. Unexpectedly, we find that Swi6 substantially increases the accessibility and dynamics of buried histone residues within a nucleosome. Restraining these dynamics impairs compaction of chromatin into liquid droplets by Swi6. Our results indicate that Swi6 couples its oligomerization to the phase separation of chromatin by a counterintuitive mechanism, namely the dynamic exposure of buried nucleosomal regions. We propose that such reshaping of the octamer core by Swi6 increases opportunities for multivalent interactions between nucleosomes, thereby promoting phase separation. This mechanism may more generally drive chromatin organization beyond heterochromatin.

Suggested Citation

  • S. Sanulli & M. J. Trnka & V. Dharmarajan & R. W. Tibble & B. D. Pascal & A. L. Burlingame & P. R. Griffin & J. D. Gross & G. J. Narlikar, 2019. "HP1 reshapes nucleosome core to promote phase separation of heterochromatin," Nature, Nature, vol. 575(7782), pages 390-394, November.
  • Handle: RePEc:nat:nature:v:575:y:2019:i:7782:d:10.1038_s41586-019-1669-2
    DOI: 10.1038/s41586-019-1669-2
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    Cited by:

    1. Naohiro Kuwayama & Tomoya Kujirai & Yusuke Kishi & Rina Hirano & Kenta Echigoya & Lingyan Fang & Sugiko Watanabe & Mitsuyoshi Nakao & Yutaka Suzuki & Kei-ichiro Ishiguro & Hitoshi Kurumizaka & Yukiko , 2023. "HMGA2 directly mediates chromatin condensation in association with neuronal fate regulation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Hyun-Soo Kim & Benjamin Roche & Sonali Bhattacharjee & Leila Todeschini & An-Yun Chang & Christopher Hammell & André Verdel & Robert A. Martienssen, 2024. "Clr4SUV39H1 ubiquitination and non-coding RNA mediate transcriptional silencing of heterochromatin via Swi6 phase separation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Wenqi Sun & Qianhua Dong & Xueqing Li & Jinxin Gao & Xianwen Ye & Chunyi Hu & Fei Li & Yong Chen, 2024. "The SUN-family protein Sad1 mediates heterochromatin spatial organization through interaction with histone H2A-H2B," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Jorge Mata-Garrido & Yao Xiang & Yunhua Chang-Marchand & Caroline Reisacher & Elisabeth Ageron & Ida Chiara Guerrera & Iñigo Casafont & Aurelia Bruneau & Claire Cherbuy & Xavier Treton & Anne Dumay & , 2022. "The Heterochromatin protein 1 is a regulator in RNA splicing precision deficient in ulcerative colitis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Beatriz del Blanco & Sergio Niñerola & Ana M. Martín-González & Juan Paraíso-Luna & Minji Kim & Rafael Muñoz-Viana & Carina Racovac & Jose V. Sanchez-Mut & Yijun Ruan & Ángel Barco, 2024. "Kdm1a safeguards the topological boundaries of PRC2-repressed genes and prevents aging-related euchromatinization in neurons," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Xiaowen Lyu & M. Jordan Rowley & Michael J. Kulik & Stephen Dalton & Victor G. Corces, 2023. "Regulation of CTCF loop formation during pancreatic cell differentiation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. 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.
    8. Jiang Zhu & Kang Chen & Yu H. Sun & Wen Ye & Juntao Liu & Dandan Zhang & Nan Su & Li Wu & Xiaochen Kou & Yanhong Zhao & Hong Wang & Shaorong Gao & Lan Kang, 2023. "LSM1-mediated Major Satellite RNA decay is required for nonequilibrium histone H3.3 incorporation into parental pronuclei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Lidice González & Daniel Kolbin & Christian Trahan & Célia Jeronimo & François Robert & Marlene Oeffinger & Kerry Bloom & Stephen W. Michnick, 2023. "Adaptive partitioning of a gene locus to the nuclear envelope in Saccharomyces cerevisiae is driven by polymer-polymer phase separation," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    10. 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.
    11. Meng Zhang & César Díaz-Celis & Jianfang Liu & Jinhui Tao & Paul D. Ashby & Carlos Bustamante & Gang Ren, 2024. "Angle between DNA linker and nucleosome core particle regulates array compaction revealed by individual-particle cryo-electron tomography," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    12. Amanda Ames & Melissa Seman & Ajay Larkin & Gulzhan Raiymbek & Ziyuan Chen & Alex Levashkevich & Bokyung Kim & Julie Suzanne Biteen & Kaushik Ragunathan, 2024. "Epigenetic memory is governed by an effector recruitment specificity toggle in Heterochromatin Protein 1," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Hua Yu & Zhen Sun & Tianyu Tan & Hongru Pan & Jing Zhao & Ling Zhang & Jiayu Chen & Anhua Lei & Yuqing Zhu & Lang Chen & Yuyan Xu & Yaxin Liu & Ming Chen & Jinghao Sheng & Zhengping Xu & Pengxu Qian &, 2021. "rRNA biogenesis regulates mouse 2C-like state by 3D structure reorganization of peri-nucleolar heterochromatin," Nature Communications, Nature, vol. 12(1), pages 1-21, December.

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