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Chemical catalyst manipulating cancer epigenome and transcription

Author

Listed:
  • Yuki Yamanashi

    (The University of Tokyo)

  • Shinpei Takamaru

    (The University of Tokyo)

  • Atsushi Okabe

    (Chiba University
    Chiba University)

  • Satoshi Kaito

    (The University of Tokyo)

  • Yuto Azumaya

    (The University of Tokyo)

  • Yugo R. Kamimura

    (The University of Tokyo)

  • Kenzo Yamatsugu

    (The University of Tokyo)

  • Tomoya Kujirai

    (The University of Tokyo)

  • Hitoshi Kurumizaka

    (The University of Tokyo)

  • Atsushi Iwama

    (The University of Tokyo)

  • Atsushi Kaneda

    (Chiba University
    Chiba University)

  • Shigehiro A. Kawashima

    (The University of Tokyo)

  • Motomu Kanai

    (The University of Tokyo)

Abstract

The number and variety of identified histone post-translational modifications (PTMs) are continually increasing. However, the specific consequences of each histone PTM remain largely unclear, primarily due to the lack of methods for selectively and rapidly introducing a desired histone PTM in living cells without genetic engineering. Here, we report the development of a cell-permeable histone acetylation catalyst, BAHA-LANA-PEG-CPP44, which selectively enters leukemia cells, binds to chromatin, and acetylates H2BK120 of endogenous histones in a short reaction time. Time-course analyses of this in-cell catalytic reaction revealed that H2BK120 acetylation attenuates the chromatin binding of negative elongation factor E (NELFE), an onco-transcription factor. This H2BK120 acetylation-mediated removal of NELFE from chromatin reshapes transcription, slows leukemia cell viability, and reduces their tumorigenic potential in mice. Therefore, this histone acetylation catalyst provides a unique tool for elucidating the time-resolved consequences of histone PTMs and may offer a modality for cancer chemotherapy.

Suggested Citation

  • Yuki Yamanashi & Shinpei Takamaru & Atsushi Okabe & Satoshi Kaito & Yuto Azumaya & Yugo R. Kamimura & Kenzo Yamatsugu & Tomoya Kujirai & Hitoshi Kurumizaka & Atsushi Iwama & Atsushi Kaneda & Shigehiro, 2025. "Chemical catalyst manipulating cancer epigenome and transcription," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56204-2
    DOI: 10.1038/s41467-025-56204-2
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    References listed on IDEAS

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    1. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    2. Wallace H. Liu & Jie Zheng & Jessica L. Feldman & Mark A. Klein & Vyacheslav I. Kuznetsov & Craig L. Peterson & Patrick R. Griffin & John M. Denu, 2020. "Multivalent interactions drive nucleosome binding and efficient chromatin deacetylation by SIRT6," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    3. Misuzu Habazaki & Shinsuke Mizumoto & Hidetoshi Kajino & Tomoya Kujirai & Hitoshi Kurumizaka & Shigehiro A. Kawashima & Kenzo Yamatsugu & Motomu Kanai, 2023. "A chemical catalyst enabling histone acylation with endogenous acyl-CoA," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Seychelle M. Vos & Lucas Farnung & Henning Urlaub & Patrick Cramer, 2018. "Structure of paused transcription complex Pol II–DSIF–NELF," Nature, Nature, vol. 560(7720), pages 601-606, August.
    5. Eisaku Kondo & Ken Saito & Yuichi Tashiro & Kaeko Kamide & Shusei Uno & Tomoko Furuya & Masao Mashita & Kiichiro Nakajima & Tomoyuki Tsumuraya & Naoya Kobayashi & Masahiro Nishibori & Mitsune Tanimoto, 2012. "Tumour lineage-homing cell-penetrating peptides as anticancer molecular delivery systems," Nature Communications, Nature, vol. 3(1), pages 1-13, January.
    6. Zhenhua Xu & Yiwen Bu & Nilesh Chitnis & Costas Koumenis & Serge Y. Fuchs & J. Alan Diehl, 2016. "miR-216b regulation of c-Jun mediates GADD153/CHOP-dependent apoptosis," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    7. Timothy J. Stasevich & Yoko Hayashi-Takanaka & Yuko Sato & Kazumitsu Maehara & Yasuyuki Ohkawa & Kumiko Sakata-Sogawa & Makio Tokunaga & Takahiro Nagase & Naohito Nozaki & James G. McNally & Hiroshi K, 2014. "Regulation of RNA polymerase II activation by histone acetylation in single living cells," Nature, Nature, vol. 516(7530), pages 272-275, December.
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