IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-48333-x.html
   My bibliography  Save this article

The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression

Author

Listed:
  • Laura A. Murray-Nerger

    (Brigham and Women’s Hospital
    Harvard Medical School
    Harvard Program in Virology
    Broad Institute of Harvard and MIT)

  • Clarisel Lozano

    (Brigham and Women’s Hospital)

  • Eric M. Burton

    (Brigham and Women’s Hospital
    Harvard Medical School
    Harvard Program in Virology
    Broad Institute of Harvard and MIT)

  • Yifei Liao

    (Brigham and Women’s Hospital
    Harvard Medical School
    Harvard Program in Virology
    Broad Institute of Harvard and MIT)

  • Nathan A. Ungerleider

    (Tulane University)

  • Rui Guo

    (Tufts University)

  • Benjamin E. Gewurz

    (Brigham and Women’s Hospital
    Harvard Medical School
    Harvard Program in Virology
    Broad Institute of Harvard and MIT)

Abstract

Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells, as well as of Kaposi’s sarcoma-associated herpesvirus in B cells, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.

Suggested Citation

  • Laura A. Murray-Nerger & Clarisel Lozano & Eric M. Burton & Yifei Liao & Nathan A. Ungerleider & Rui Guo & Benjamin E. Gewurz, 2024. "The nucleic acid binding protein SFPQ represses EBV lytic reactivation by promoting histone H1 expression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48333-x
    DOI: 10.1038/s41467-024-48333-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-48333-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-48333-x?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. Michael A. Willcockson & Sean E. Healton & Cary N. Weiss & Boris A. Bartholdy & Yair Botbol & Laxmi N. Mishra & Dhruv S. Sidhwani & Tommy J. Wilson & Hugo B. Pinto & Maxim I. Maron & Karin A. Skalina , 2021. "H1 histones control the epigenetic landscape by local chromatin compaction," Nature, Nature, vol. 589(7841), pages 293-298, January.
    2. Melody A. Lever & John P. H. Th'ng & Xuejun Sun & Michael J. Hendzel, 2000. "Rapid exchange of histone H1.1 on chromatin in living human cells," Nature, Nature, vol. 408(6814), pages 873-876, December.
    3. Silvia Bottini & Nedra Hamouda-Tekaya & Raphael Mategot & Laure-Emmanuelle Zaragosi & Stephane Audebert & Sabrina Pisano & Valerie Grandjean & Claire Mauduit & Mohamed Benahmed & Pascal Barbry & Emanu, 2017. "Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    4. Nevin Yusufova & Andreas Kloetgen & Matt Teater & Adewola Osunsade & Jeannie M. Camarillo & Christopher R. Chin & Ashley S. Doane & Bryan J. Venters & Stephanie Portillo-Ledesma & Joseph Conway & Jude, 2021. "Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture," Nature, Nature, vol. 589(7841), pages 299-305, January.
    5. Tom Misteli & Akash Gunjan & Robert Hock & Michael Bustin & David T. Brown, 2000. "Dynamic binding of histone H1 to chromatin in living cells," Nature, Nature, vol. 408(6814), pages 877-881, December.
    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. Cuifang Liu & Juan Yu & Aoqun Song & Min Wang & Jiansen Hu & Ping Chen & Jicheng Zhao & Guohong Li, 2023. "Histone H1 facilitates restoration of H3K27me3 during DNA replication by chromatin compaction," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yangmian Yuan & Yu Fan & Yihao Zhou & Rong Qiu & Wei Kang & Yu Liu & Yuchen Chen & Chenyu Wang & Jiajian Shi & Chengyu Liu & Yangkai Li & Min Wu & Kun Huang & Yong Liu & Ling Zheng, 2023. "Linker histone variant H1.2 is a brake on white adipose tissue browning," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Rina Hirano & Haruhiko Ehara & Tomoya Kujirai & Tamami Uejima & Yoshimasa Takizawa & Shun-ichi Sekine & Hitoshi Kurumizaka, 2022. "Structural basis of RNA polymerase II transcription on the chromatosome containing linker histone H1," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Ko Sato & Amarjeet Kumar & Keisuke Hamada & Chikako Okada & Asako Oguni & Ayumi Machiyama & Shun Sakuraba & Tomohiro Nishizawa & Osamu Nureki & Hidetoshi Kono & Kazuhiro Ogata & Toru Sengoku, 2021. "Structural basis of the regulation of the normal and oncogenic methylation of nucleosomal histone H3 Lys36 by NSD2," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. 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.
    6. 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.
    7. Carlos Contreras & Minaya Villasana & Michael J Hendzel & Gustavo Carrero, 2018. "Using a model comparison approach to describe the assembly pathway for histone H1," PLOS ONE, Public Library of Science, vol. 13(1), pages 1-21, January.
    8. Jiahong Li & Gerald J. Shami & Ellie Cho & Boyin Liu & Eric Hanssen & Matthew W. A. Dixon & Leann Tilley, 2022. "Repurposing the mitotic machinery to drive cellular elongation and chromatin reorganisation in Plasmodium falciparum gametocytes," Nature Communications, Nature, vol. 13(1), pages 1-15, 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_s41467-024-48333-x. 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.