IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-29541-9.html
   My bibliography  Save this article

STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming

Author

Listed:
  • Zhaowei Chu

    (Massachusetts General Hospital and Harvard Medical School
    The Second Hospital Affiliated to Xi’an Jiaotong University)

  • Lei Gu

    (Max Planck Institute for Heart and Lung Research)

  • Yeguang Hu

    (Massachusetts General Hospital and Harvard Medical School)

  • Xiaoyang Zhang

    (Fudan University)

  • Man Li

    (Massachusetts General Hospital and Harvard Medical School)

  • Jiajia Chen

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Da Teng

    (Massachusetts General Hospital and Harvard Medical School)

  • Man Huang

    (Harvard Medical School)

  • Che-Hung Shen

    (National Health Research Institutes)

  • Li Cai

    (University of Texas MD Anderson Cancer Center)

  • Toshimi Yoshida

    (Massachusetts General Hospital and Harvard Medical School)

  • Yifeng Qi

    (Massachusetts Institute of Technology)

  • Zhixin Niu

    (Max Planck Institute for Heart and Lung Research)

  • Austin Feng

    (Massachusetts General Hospital and Harvard Medical School)

  • Songmei Geng

    (The Second Hospital Affiliated to Xi’an Jiaotong University)

  • Dennie T. Frederick

    (Massachusetts General Hospital Cancer Center)

  • Emma Specht

    (Massachusetts General Hospital Cancer Center)

  • Adriano Piris

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Ryan J. Sullivan

    (Massachusetts General Hospital Cancer Center)

  • Keith T. Flaherty

    (Massachusetts General Hospital Cancer Center)

  • Genevieve M. Boland

    (Massachusetts General Hospital)

  • Katia Georgopoulos

    (Massachusetts General Hospital and Harvard Medical School)

  • David Liu

    (Dana-Farber Cancer Institute
    Broad Institute of MIT and Harvard)

  • Yang Shi

    (Harvard Medical School
    Oxford University)

  • Bin Zheng

    (Massachusetts General Hospital and Harvard Medical School)

Abstract

The cohesin complex participates in the organization of 3D genome through generating and maintaining DNA loops. Stromal antigen 2 (STAG2), a core subunit of the cohesin complex, is frequently mutated in various cancers. However, the impact of STAG2 inactivation on 3D genome organization, especially the long-range enhancer-promoter contacts and subsequent gene expression control in cancer, remains poorly understood. Here we show that depletion of STAG2 in melanoma cells leads to expansion of topologically associating domains (TADs) and enhances the formation of acetylated histone H3 lysine 27 (H3K27ac)-associated DNA loops at sites where binding of STAG2 is switched to its paralog STAG1. We further identify Interferon Regulatory Factor 9 (IRF9) as a major direct target of STAG2 in melanoma cells via integrated RNA-seq, STAG2 ChIP-seq and H3K27ac HiChIP analyses. We demonstrate that loss of STAG2 activates IRF9 through modulating the 3D genome organization, which in turn enhances type I interferon signaling and increases the expression of PD-L1. Our findings not only establish a previously unknown role of the STAG2 to STAG1 switch in 3D genome organization, but also reveal a functional link between STAG2 and interferon signaling in cancer cells, which may enhance the immune evasion potential in STAG2-mutant cancer.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29541-9
    DOI: 10.1038/s41467-022-29541-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-29541-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-29541-9?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. Wibke Schwarzer & Nezar Abdennur & Anton Goloborodko & Aleksandra Pekowska & Geoffrey Fudenberg & Yann Loe-Mie & Nuno A Fonseca & Wolfgang Huber & Christian H. Haering & Leonid Mirny & Francois Spitz, 2017. "Two independent modes of chromatin organization revealed by cohesin removal," Nature, Nature, vol. 551(7678), pages 51-56, November.
    2. 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. 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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. 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.
    9. Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Andrea Fontana & Francesca Vercellone & Mattia Conte & Mario Nicodemi, 2024. "Multiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    10. 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.
    11. 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.
    12. 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.
    13. 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.
    14. Julia Minderjahn & Alexander Fischer & Konstantin Maier & Karina Mendes & Margit Nuetzel & Johanna Raithel & Hanna Stanewsky & Ute Ackermann & Robert Månsson & Claudia Gebhard & Michael Rehli, 2022. "Postmitotic differentiation of human monocytes requires cohesin-structured chromatin," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. 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.
    16. Mario Ivanković & Jeremias N. Brand & Luca Pandolfini & Thomas Brown & Martin Pippel & Andrei Rozanski & Til Schubert & Markus A. Grohme & Sylke Winkler & Laura Robledillo & Meng Zhang & Azzurra Codin, 2024. "A comparative analysis of planarian genomes reveals regulatory conservation in the face of rapid structural divergence," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    17. Li-Hsin Chang & Sourav Ghosh & Andrea Papale & Jennifer M. Luppino & Mélanie Miranda & Vincent Piras & Jéril Degrouard & Joanne Edouard & Mallory Poncelet & Nathan Lecouvreur & Sébastien Bloyer & Amél, 2023. "Multi-feature clustering of CTCF binding creates robustness for loop extrusion blocking and Topologically Associating Domain boundaries," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    18. Botong Zhou & Ping Hu & Guichun Liu & Zhou Chang & Zhiwei Dong & Zihe Li & Yuan Yin & Zunzhe Tian & Ge Han & Wen Wang & Xueyan Li, 2024. "Evolutionary patterns and functional effects of 3D chromatin structures in butterflies with extensive genome rearrangements," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    19. 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.
    20. Yufan Zhou & Tian Li & Lavanya Choppavarapu & Kun Fang & Shili Lin & Victor X. Jin, 2024. "Integration of scHi-C and scRNA-seq data defines distinct 3D-regulated and biological-context dependent cell subpopulations," Nature Communications, Nature, vol. 15(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:13:y:2022:i:1:d:10.1038_s41467-022-29541-9. 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.