IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46857-w.html
   My bibliography  Save this article

GAS41 modulates ferroptosis by anchoring NRF2 on chromatin

Author

Listed:
  • Zhe Wang

    (Columbia University)

  • Xin Yang

    (Columbia University)

  • Delin Chen

    (Columbia University)

  • Yanqing Liu

    (Columbia University)

  • Zhiming Li

    (Columbia University)

  • Shoufu Duan

    (Columbia University)

  • Zhiguo Zhang

    (Columbia University
    Columbia University
    Columbia University
    Columbia University)

  • Xuejun Jiang

    (Memorial Sloan-Kettering Cancer Center)

  • Brent R. Stockwell

    (Columbia University
    Columbia University)

  • Wei Gu

    (Columbia University
    Columbia University
    Columbia University)

Abstract

YEATS domain-containing protein GAS41 is a histone reader and oncogene. Here, through genome-wide CRISPR-Cas9 screenings, we identify GAS41 as a repressor of ferroptosis. GAS41 interacts with NRF2 and is critical for NRF2 to activate its targets such as SLC7A11 for modulating ferroptosis. By recognizing the H3K27-acetylation (H3K27-ac) marker, GAS41 is recruited to the SLC7A11 promoter, independent of NRF2 binding. By bridging the interaction between NRF2 and the H3K27-ac marker, GAS41 acts as an anchor for NRF2 on chromatin in a promoter-specific manner for transcriptional activation. Moreover, the GAS41-mediated effect on ferroptosis contributes to its oncogenic role in vivo. These data demonstrate that GAS41 is a target for modulating tumor growth through ferroptosis. Our study reveals a mechanism for GAS41-mediated regulation in transcription by anchoring NRF2 on chromatin, and provides a model in which the DNA binding activity on chromatin by transcriptional factors (NRF2) can be directly regulated by histone markers (H3K27-ac).

Suggested Citation

  • Zhe Wang & Xin Yang & Delin Chen & Yanqing Liu & Zhiming Li & Shoufu Duan & Zhiguo Zhang & Xuejun Jiang & Brent R. Stockwell & Wei Gu, 2024. "GAS41 modulates ferroptosis by anchoring NRF2 on chromatin," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46857-w
    DOI: 10.1038/s41467-024-46857-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46857-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-46857-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. Liling Wan & Hong Wen & Yuanyuan Li & Jie Lyu & Yuanxin Xi & Takayuki Hoshii & Julia K. Joseph & Xiaolu Wang & Yong-Hwee E. Loh & Michael A. Erb & Amanda L. Souza & James E. Bradner & Li Shen & Wei Li, 2017. "ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia," Nature, Nature, vol. 543(7644), pages 265-269, March.
    2. Wenyi Mi & Haipeng Guan & Jie Lyu & Dan Zhao & Yuanxin Xi & Shiming Jiang & Forest H. Andrews & Xiaolu Wang & Mihai Gagea & Hong Wen & Laszlo Tora & Sharon Y. R. Dent & Tatiana G. Kutateladze & Wei Li, 2017. "YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    3. Le Jiang & Ning Kon & Tongyuan Li & Shang-Jui Wang & Tao Su & Hanina Hibshoosh & Richard Baer & Wei Gu, 2015. "Ferroptosis as a p53-mediated activity during tumour suppression," Nature, Nature, vol. 520(7545), pages 57-62, April.
    4. Sebastian Doll & Florencio Porto Freitas & Ron Shah & Maceler Aldrovandi & Milene Costa Silva & Irina Ingold & Andrea Goya Grocin & Thamara Nishida Xavier da Silva & Elena Panzilius & Christina H. Sch, 2019. "FSP1 is a glutathione-independent ferroptosis suppressor," Nature, Nature, vol. 575(7784), pages 693-698, November.
    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. Yandi Wu & Tongsheng Huang & Xinghui Li & Conghui Shen & Honglin Ren & Haiping Wang & Teng Wu & Xinlu Fu & Shijie Deng & Ziqi Feng & Shijie Xiong & Hui Li & Saifei Gao & Zhenyu Yang & Fei Gao & Lele D, 2023. "Retinol dehydrogenase 10 reduction mediated retinol metabolism disorder promotes diabetic cardiomyopathy in male mice," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Dadi Jiang & Youming Guo & Tianyu Wang & Liang Wang & Yuelong Yan & Ling Xia & Rakesh Bam & Zhifen Yang & Hyemin Lee & Takao Iwawaki & Boyi Gan & Albert C. Koong, 2024. "IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Pranavi Koppula & Guang Lei & Yilei Zhang & Yuelong Yan & Chao Mao & Lavanya Kondiparthi & Jiejun Shi & Xiaoguang Liu & Amber Horbath & Molina Das & Wei Li & Masha V. Poyurovsky & Kellen Olszewski & B, 2022. "A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Bartosz Wiernicki & Sophia Maschalidi & Jonathan Pinney & Sandy Adjemian & Tom Vanden Berghe & Kodi S. Ravichandran & Peter Vandenabeele, 2022. "Cancer cells dying from ferroptosis impede dendritic cell-mediated anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    5. Di-Yang Sun & Wen-Bin Wu & Jian-Jin Wu & Yu Shi & Jia-Jun Xu & Shen-Xi Ouyang & Chen Chi & Yi Shi & Qing-Xin Ji & Jin-Hao Miao & Jiang-Tao Fu & Jie Tong & Ping-Ping Zhang & Jia-Bao Zhang & Zhi-Yong Li, 2024. "Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    6. Shaela Wright & Xujie Zhao & Wojciech Rosikiewicz & Shelby Mryncza & Judith Hyle & Wenjie Qi & Zhenling Liu & Siqi Yi & Yong Cheng & Beisi Xu & Chunliang Li, 2023. "Systematic characterization of the HOXA9 downstream targets in MLL-r leukemia by noncoding CRISPR screens," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Gang Liu & Jian-ying Ma & Gang Hu & Huan Jin, 2021. "Identification and validation of a novel ferroptosis-related gene model for predicting the prognosis of gastric cancer patients," PLOS ONE, Public Library of Science, vol. 16(7), pages 1-16, July.
    8. Yuelong Yan & Hongqi Teng & Qinglei Hang & Lavanya Kondiparthi & Guang Lei & Amber Horbath & Xiaoguang Liu & Chao Mao & Shiqi Wu & Li Zhuang & M. James You & Masha V. Poyurovsky & Li Ma & Kellen Olsze, 2023. "SLC7A11 expression level dictates differential responses to oxidative stress in cancer cells," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Wei Yang & Bo Mu & Jing You & Chenyu Tian & Huachao Bin & Zhiqiang Xu & Liting Zhang & Ronggang Ma & Ming Wu & Guo Zhang & Chong Huang & Linli Li & Zhenhua Shao & Lunzhi Dai & Laurent Désaubry & Sheng, 2022. "Non-classical ferroptosis inhibition by a small molecule targeting PHB2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Jingjie Yi & Omid Tavana & Huan Li & Donglai Wang & Richard J. Baer & Wei Gu, 2023. "Targeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Nathan P. Ward & Sang Jun Yoon & Tyce Flynn & Amanda M. Sherwood & Maddison A. Olley & Juliana Madej & Gina M. DeNicola, 2024. "Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    12. Yun Lv & Chunhui Liang & Qichao Sun & Jing Zhu & Haiyan Xu & Xiaoqing Li & Yao-yao Li & Qihai Wang & Huiqing Yuan & Bo Chu & Deyu Zhu, 2023. "Structural insights into FSP1 catalysis and ferroptosis inhibition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    13. Jun Jiang & Lili Yang & Qianqian Xie & Xi Liu & Jie Jiang & Jie Zhang & Shuping Zhang & Huizhen Zheng & Wenjie Li & Xiaoming Cai & Sijin Liu & Ruibin Li, 2024. "Synthetic vectors for activating the driving axis of ferroptosis," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    14. Zifan Ye & Lei Fu & Shuangyu Li & Ziying Chen & Jianhong Ouyang & Xinci Shang & Yanli Liu & Lianghui Gao & Yipeng Wang, 2024. "Synergistic collaboration between AMPs and non-direct antimicrobial cationic peptides," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    15. Steffen Mueller & Gail Dennison & Shujun Liu, 2021. "An Assessment on Ethanol-Blended Gasoline/Diesel Fuels on Cancer Risk and Mortality," IJERPH, MDPI, vol. 18(13), pages 1-23, June.
    16. Samya Van Coillie & Emily Van San & Ines Goetschalckx & Bartosz Wiernicki & Banibrata Mukhopadhyay & Wulf Tonnus & Sze Men Choi & Ria Roelandt & Catalina Dumitrascu & Ludwig Lamberts & Geert Dams & Wa, 2022. "Targeting ferroptosis protects against experimental (multi)organ dysfunction and death," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    17. Derek H. Janssens & Melodie Duran & Dominik J. Otto & Weifang Wu & Yiling Xu & Danielle Kirkey & Charles G. Mullighan & Joanna S. Yi & Soheil Meshinchi & Jay F. Sarthy & Kami Ahmad & Steven Henikoff, 2024. "MLL oncoprotein levels influence leukemia lineage identities," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    18. Giovanni Tosi & Alessandro Paoli & Gaia Zuccolotto & Emilia Turco & Manuela Simonato & Daniela Tosoni & Francesco Tucci & Pietro Lugato & Monica Giomo & Nicola Elvassore & Antonio Rosato & Paola Cogo , 2024. "Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    19. Juliane Tschuck & Lea Theilacker & Ina Rothenaigner & Stefanie A. I. Weiß & Banu Akdogan & Van Thanh Lam & Constanze Müller & Roman Graf & Stefanie Brandner & Christian Pütz & Tamara Rieder & Philippe, 2023. "Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Ming-liang Ji & Hua Jiang & Zhuang Li & Rui Geng & Jun Zheng Hu & Yu Cheng Lin & Jun Lu, 2022. "Sirt6 attenuates chondrocyte senescence and osteoarthritis progression," Nature Communications, Nature, vol. 13(1), pages 1-18, 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_s41467-024-46857-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.