IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-43869-w.html
   My bibliography  Save this article

Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops

Author

Listed:
  • Daniel Bsteh

    (Vienna BioCenter (VBC)
    Doctoral School of the University of Vienna and Medical University of Vienna
    University of Southern California
    University of Southern California)

  • Hagar F. Moussa

    (Vienna BioCenter (VBC)
    Doctoral School of the University of Vienna and Medical University of Vienna
    Boston University)

  • Georg Michlits

    (Vienna BioCenter (VBC)
    Doctoral School of the University of Vienna and Medical University of Vienna
    JLP Health GmbH)

  • Ramesh Yelagandula

    (Vienna BioCenter (VBC)
    Centre for DNA Fingerprinting and Diagnostics (CDFD), Uppal)

  • Jingkui Wang

    (Vienna BioCenter (VBC)
    Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC))

  • Ulrich Elling

    (Vienna BioCenter (VBC))

  • Oliver Bell

    (Vienna BioCenter (VBC)
    University of Southern California)

Abstract

Polycomb Repressive Complexes 1 and 2 (PRC1, PRC2) are conserved epigenetic regulators that promote transcriptional gene silencing. PRC1 and PRC2 converge on shared targets, catalyzing repressive histone modifications. Additionally, a subset of PRC1/PRC2 targets engage in long-range interactions whose functions in gene silencing are poorly understood. Using a CRISPR screen in mouse embryonic stem cells, we found that the cohesin regulator PDS5A links transcriptional silencing by Polycomb and 3D genome organization. PDS5A deletion impairs cohesin unloading and results in derepression of a subset of endogenous PRC1/PRC2 target genes. Importantly, derepression is not linked to loss of Polycomb chromatin domains. Instead, PDS5A removal causes aberrant cohesin activity leading to ectopic insulation sites, which disrupt the formation of ultra-long Polycomb loops. We show that these loops are important for robust silencing at a subset of PRC1/PRC2 target genes and that maintenance of cohesin-dependent genome architecture is critical for Polycomb regulation.

Suggested Citation

  • Daniel Bsteh & Hagar F. Moussa & Georg Michlits & Ramesh Yelagandula & Jingkui Wang & Ulrich Elling & Oliver Bell, 2023. "Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43869-w
    DOI: 10.1038/s41467-023-43869-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-43869-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-43869-w?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. Antonio Tedeschi & Gordana Wutz & Sébastien Huet & Markus Jaritz & Annelie Wuensche & Erika Schirghuber & Iain Finley Davidson & Wen Tang & David A. Cisneros & Venugopal Bhaskara & Tomoko Nishiyama & , 2013. "Wapl is an essential regulator of chromatin structure and chromosome segregation," Nature, Nature, vol. 501(7468), pages 564-568, September.
    2. Christian H. Haering & Ana-Maria Farcas & Prakash Arumugam & Jean Metson & Kim Nasmyth, 2008. "The cohesin ring concatenates sister DNA molecules," Nature, Nature, vol. 454(7202), pages 297-301, July.
    3. Georg A. Busslinger & Roman R. Stocsits & Petra van der Lelij & Elin Axelsson & Antonio Tedeschi & Niels Galjart & Jan-Michael Peters, 2017. "Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl," Nature, Nature, vol. 544(7651), pages 503-507, April.
    4. Hengbin Wang & Liangjun Wang & Hediye Erdjument-Bromage & Miguel Vidal & Paul Tempst & Richard S. Jones & Yi Zhang, 2004. "Role of histone H2A ubiquitination in Polycomb silencing," Nature, Nature, vol. 431(7010), pages 873-878, October.
    5. Ho Lam Chan & Felipe Beckedorff & Yusheng Zhang & Jenaro Garcia-Huidobro & Hua Jiang & Antonio Colaprico & Daniel Bilbao & Maria E. Figueroa & John LaCava & Ramin Shiekhattar & Lluis Morey, 2018. "Polycomb complexes associate with enhancers and promote oncogenic transcriptional programs in cancer through multiple mechanisms," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    6. Haojie Li & Robert Liefke & Junyi Jiang & Jesse Vigoda Kurland & Wei Tian & Pujuan Deng & Weidi Zhang & Qian He & Dinshaw J. Patel & Martha L. Bulyk & Yang Shi & Zhanxin Wang, 2017. "Polycomb-like proteins link the PRC2 complex to CpG islands," Nature, Nature, vol. 549(7671), pages 287-291, September.
    7. Yuko Katoh-Fukui & Reiko Tsuchiya & Toshihiko Shiroishi & Yoko Nakahara & Naoko Hashimoto & Kousei Noguchi & Toru Higashinakagawa, 1998. "Male-to-female sex reversal in M33 mutant mice," Nature, Nature, vol. 393(6686), pages 688-692, June.
    8. 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.
    9. Ulrich Elling & Reiner A. Wimmer & Andreas Leibbrandt & Thomas Burkard & Georg Michlits & Alexandra Leopoldi & Thomas Micheler & Dana Abdeen & Sergei Zhuk & Irene M. Aspalter & Cornelia Handl & Julia , 2017. "A reversible haploid mouse embryonic stem cell biobank resource for functional genomics," Nature, Nature, vol. 550(7674), pages 114-118, October.
    10. Michael H. Kagey & Jamie J. Newman & Steve Bilodeau & Ye Zhan & David A. Orlando & Nynke L. van Berkum & Christopher C. Ebmeier & Jesse Goossens & Peter B. Rahl & Stuart S. Levine & Dylan J. Taatjes &, 2010. "Mediator and cohesin connect gene expression and chromatin architecture," Nature, Nature, vol. 467(7314), pages 430-435, September.
    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. Ryuichiro Nakato & Toyonori Sakata & Jiankang Wang & Luis Augusto Eijy Nagai & Yuya Nagaoka & Gina Miku Oba & Masashige Bando & Katsuhiko Shirahige, 2023. "Context-dependent perturbations in chromatin folding and the transcriptome by cohesin and related factors," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Mengwen Hu & Yu-Han Yeh & Yasuhisa Munakata & Hironori Abe & Akihiko Sakashita & So Maezawa & Miguel Vidal & Haruhiko Koseki & Neil Hunter & Richard M. Schultz & Satoshi H. Namekawa, 2022. "PRC1-mediated epigenetic programming is required to generate the ovarian reserve," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    3. 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.
    4. Jiankang Wang & Masashige Bando & Katsuhiko Shirahige & Ryuichiro Nakato, 2022. "Large-scale multi-omics analysis suggests specific roles for intragenic cohesin in transcriptional regulation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Judith H. I. Haarhuis & Robin H. Weide & Vincent A. Blomen & Koen D. Flach & Hans Teunissen & Laureen Willems & Thijn R. Brummelkamp & Benjamin D. Rowland & Elzo Wit, 2022. "A Mediator-cohesin axis controls heterochromatin domain formation," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. 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.
    7. Wenjing Yan & Yongwang Zhong & Xin Hu & Tuan Xu & Yinghua Zhang & Stephen Kales & Yanyan Qu & Daniel C. Talley & Bolormaa Baljinnyam & Christopher A. LeClair & Anton Simeonov & Brian M. Polster & Ruil, 2023. "Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    8. Evelyn Kabirova & Anastasiya Ryzhkova & Varvara Lukyanchikova & Anna Khabarova & Alexey Korablev & Tatyana Shnaider & Miroslav Nuriddinov & Polina Belokopytova & Alexander Smirnov & Nikita V. Khotskin, 2024. "TAD border deletion at the Kit locus causes tissue-specific ectopic activation of a neighboring gene," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. 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.
    10. 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.
    11. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Alexandra D’Oto & Jie Fang & Hongjian Jin & Beisi Xu & Shivendra Singh & Anoushka Mullasseril & Victoria Jones & Ahmed Abu-Zaid & Xinyu Buttlar & Bailey Cooke & Dongli Hu & Jason Shohet & Andrew J. Mu, 2021. "KDM6B promotes activation of the oncogenic CDK4/6-pRB-E2F pathway by maintaining enhancer activity in MYCN-amplified neuroblastoma," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    13. Jie Zhao & Meng Zhang & Wenyan Hui & Yue Zhang & Jing Wang & Shaojing Wang & Lai-Yu Kwok & Jian Kong & Heping Zhang & Wenyi Zhang, 2023. "Roles of adenine methylation in the physiology of Lacticaseibacillus paracasei," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    14. Xinyi Chen & Yiran Guo & Ting Zhao & Jiuwei Lu & Jian Fang & Yinsheng Wang & Gang Greg Wang & Jikui Song, 2024. "Structural basis for the H2AK119ub1-specific DNMT3A-nucleosome interaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. 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.
    16. Koon-Kiu Yan & Shaoke Lou & Mark Gerstein, 2017. "MrTADFinder: A network modularity based approach to identify topologically associating domains in multiple resolutions," PLOS Computational Biology, Public Library of Science, vol. 13(7), pages 1-22, July.
    17. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    18. 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.
    19. Ayantika Sen Gupta & Chris Seidel & Dai Tsuchiya & Sean McKinney & Zulin Yu & Sarah E. Smith & Jay R. Unruh & Jennifer L. Gerton, 2023. "Defining a core configuration for human centromeres during mitosis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Anna Worthmann & Julius Ridder & Sharlaine Y. L. Piel & Ioannis Evangelakos & Melina Musfeldt & Hannah Voß & Marie O’Farrell & Alexander W. Fischer & Sangeeta Adak & Monica Sundd & Hasibullah Siffeti , 2024. "Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use," Nature Communications, Nature, vol. 15(1), pages 1-13, 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_s41467-023-43869-w. 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.