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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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