IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43480-z.html
   My bibliography  Save this article

Phase-separated CCER1 coordinates the histone-to-protamine transition and male fertility

Author

Listed:
  • Dongdong Qin

    (Nanjing Medical University)

  • Yayun Gu

    (Nanjing Medical University
    Nanjing Medical University)

  • Yu Zhang

    (Tsinghua University
    Tsinghua-Peking Center for Life Sciences
    Fudan University
    Chinese Academy of Medical Sciences)

  • Shu Wang

    (Nanjing Medical University)

  • Tao Jiang

    (Nanjing Medical University
    Nanjing Medical University)

  • Yao Wang

    (Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Cheng Wang

    (Nanjing Medical University
    Nanjing Medical University)

  • Chang Chen

    (Nanjing Medical University)

  • Tao Zhang

    (Nanjing Medical University)

  • Weiya Xu

    (Nanjing Medical University)

  • Hanben Wang

    (Nanjing Medical University)

  • Ke Zhang

    (Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Liangjun Hu

    (Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Lufan Li

    (Nanjing Medical University)

  • Wei Xie

    (Tsinghua University
    Tsinghua-Peking Center for Life Sciences)

  • Xin Wu

    (Nanjing Medical University)

  • Zhibin Hu

    (Nanjing Medical University
    Nanjing Medical University)

Abstract

Idiopathic fertility disorders are associated with mutations in various genes. Here, we report that coiled-coil glutamate-rich protein 1 (CCER1), a germline-specific and intrinsically disordered protein (IDP), mediates postmeiotic spermatid differentiation. In contrast, CCER1 deficiency results in defective sperm chromatin compaction and infertility in mice. CCER1 increases transition protein (Tnp1/2) and protamine (Prm1/2) transcription and mediates multiple histone epigenetic modifications during the histone-to-protamine (HTP) transition. Immiscible with heterochromatin in the nucleus, CCER1 self-assembles into a polymer droplet and forms a liquid-liquid phase-separated condensate in the nucleus. Notably, we identified loss-of-function (LoF) variants of human CCER1 (hCCER1) in five patients with nonobstructive azoospermia (NOA) that were absent in 2713 fertile controls. The mutants led to premature termination or frameshift in CCER1 translation, and disrupted condensates in vitro. In conclusion, we propose that nuclear CCER1 is a phase-separated condensate that links histone epigenetic modifications, HTP transitions, chromatin condensation, and male fertility.

Suggested Citation

  • Dongdong Qin & Yayun Gu & Yu Zhang & Shu Wang & Tao Jiang & Yao Wang & Cheng Wang & Chang Chen & Tao Zhang & Weiya Xu & Hanben Wang & Ke Zhang & Liangjun Hu & Lufan Li & Wei Xie & Xin Wu & Zhibin Hu, 2023. "Phase-separated CCER1 coordinates the histone-to-protamine transition and male fertility," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43480-z
    DOI: 10.1038/s41467-023-43480-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43480-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43480-z?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. Charles H. Li & Eliot L. Coffey & Alessandra Dall’Agnese & Nancy M. Hannett & Xin Tang & Jonathan E. Henninger & Jesse M. Platt & Ozgur Oksuz & Alicia V. Zamudio & Lena K. Afeyan & Jurian Schuijers & , 2020. "MeCP2 links heterochromatin condensates and neurodevelopmental disease," Nature, Nature, vol. 586(7829), pages 440-444, October.
    2. Laura D. Gallego & Maren Schneider & Chitvan Mittal & Anete Romanauska & Ricardo M. Gudino Carrillo & Tobias Schubert & B. Franklin Pugh & Alwin Köhler, 2020. "Phase separation directs ubiquitination of gene-body nucleosomes," Nature, Nature, vol. 579(7800), pages 592-597, March.
    3. Yuki Okada & Greg Scott & Manas K. Ray & Yuji Mishina & Yi Zhang, 2007. "Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis," Nature, Nature, vol. 450(7166), pages 119-123, November.
    4. Emily Crane & Qian Bian & Rachel Patton McCord & Bryan R. Lajoie & Bayly S. Wheeler & Edward J. Ralston & Satoru Uzawa & Job Dekker & Barbara J. Meyer, 2015. "Condensin-driven remodelling of X chromosome topology during dosage compensation," Nature, Nature, vol. 523(7559), pages 240-244, 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. Zhen-Hui Wang & Xin-Feng Wang & Tianyuan Lu & Ming-Rui Li & Peng Jiang & Jing Zhao & Si-Tong Liu & Xue-Qi Fu & Jonathan F. Wendel & Yves Peer & Bao Liu & Lin-Feng Li, 2022. "Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. 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.
    3. Brent S. Perlman & Noah Burget & Yeqiao Zhou & Gregory W. Schwartz & Jelena Petrovic & Zora Modrusan & Robert B. Faryabi, 2024. "Enhancer-promoter hubs organize transcriptional networks promoting oncogenesis and drug resistance," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    4. Wu Zuo & Guangming Chen & Zhimei Gao & Shuai Li & Yanyan Chen & Chenhui Huang & Juan Chen & Zhengjun Chen & Ming Lei & Qian Bian, 2021. "Stage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    5. Mingsen Li & Huaxing Huang & Bofeng Wang & Shaoshuai Jiang & Huizhen Guo & Liqiong Zhu & Siqi Wu & Jiafeng Liu & Li Wang & Xihong Lan & Wang Zhang & Jin Zhu & Fuxi Li & Jieying Tan & Zhen Mao & Chunqi, 2022. "Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Bob Zimmermann & Juan D. Montenegro & Sofia M. C. Robb & Whitney J. Fropf & Lukas Weilguny & Shuonan He & Shiyuan Chen & Jessica Lovegrove-Walsh & Eric M. Hill & Cheng-Yi Chen & Katerina Ragkousi & Da, 2023. "Topological structures and syntenic conservation in sea anemone genomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Daniela Michelatti & Sven Beyes & Chiara Bernardis & Maria Luce Negri & Leonardo Morelli & Naiara Garcia Bediaga & Vittoria Poli & Luca Fagnocchi & Sara Lago & Sarah D’Annunzio & Nicole Cona & Ilaria , 2024. "Oncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    8. François Serra & Andrea Nieto-Aliseda & Lucía Fanlo-Escudero & Llorenç Rovirosa & Mónica Cabrera-Pasadas & Aleksey Lazarenkov & Blanca Urmeneta & Alvaro Alcalde-Merino & Emanuele M. Nola & Andrei L. O, 2024. "p53 rapidly restructures 3D chromatin organization to trigger a transcriptional response," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Jacques Serizay & Cyril Matthey-Doret & Amaury Bignaud & Lyam Baudry & Romain Koszul, 2024. "Orchestrating chromosome conformation capture analysis with Bioconductor," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    10. Yanlin Zhang & Mathieu Blanchette, 2022. "Reference panel guided topological structure annotation of Hi-C data," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Olivier Messina & Flavien Raynal & Julian Gurgo & Jean-Bernard Fiche & Vera Pancaldi & Marcelo Nollmann, 2023. "3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Bobae Yang & Sueun Kim & Woong-Jae Jung & Kyungwoo Kim & Sugyung Kim & Yong-Jin Kim & Tae-Gyun Kim & Eun-Chong Lee & Jung-Sik Joo & Chae Gyu Park & Sumin Oh & Kyung Hyun Yoo & Hyoung-Pyo Kim, 2023. "CTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    13. 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.
    14. Dadong Dai & Chuanshuai Xie & Yayi Zhou & Dexin Bo & Shurong Zhang & Shengqiang Mao & Yucheng Liao & Simeng Cui & Zhaolu Zhu & Xueyu Wang & Fanling Li & Donghai Peng & Jinshui Zheng & Ming Sun, 2023. "Unzipped chromosome-level genomes reveal allopolyploid nematode origin pattern as unreduced gamete hybridization," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. 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.
    16. Raphaël Pantier & Megan Brown & Sicheng Han & Katie Paton & Stephen Meek & Thomas Montavon & Nicholas Shukeir & Toni McHugh & David A. Kelly & Tino Hochepied & Claude Libert & Thomas Jenuwein & Tom Bu, 2024. "MeCP2 binds to methylated DNA independently of phase separation and heterochromatin organisation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    17. 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.
    18. Ji Min Lee & Henrik M. Hammarén & Mikhail M. Savitski & Sung Hee Baek, 2023. "Control of protein stability by post-translational modifications," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    19. Chong Wang & Xiang Liu & Jun Liang & Yohei Narita & Weiyue Ding & Difei Li & Luyao Zhang & Hongbo Wang & Merrin Man Long Leong & Isabella Hou & Catherine Gerdt & Chang Jiang & Qian Zhong & Zhonghui Ta, 2023. "A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    20. Zhaowei Chu & Lei Gu & Yeguang Hu & Xiaoyang Zhang & Man Li & Jiajia Chen & Da Teng & Man Huang & Che-Hung Shen & Li Cai & Toshimi Yoshida & Yifeng Qi & Zhixin Niu & Austin Feng & Songmei Geng & Denni, 2022. "STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming," 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:14:y:2023:i:1:d:10.1038_s41467-023-43480-z. 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.