System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Epublish 1 citation

PubMed: 39856033 DOI: 10.1038/s41467-025-56204-2

Chemical catalyst manipulating cancer epigenome and transcription.

Nat Commun 16(1):887

Authors: Yuki Yamanashi, Shinpei Takamaru, Atsushi Okabe, Satoshi Kaito, Yuto Azumaya, Yugo R Kamimura, Kenzo Yamatsugu, Tomoya Kujirai, Hitoshi Kurumizaka, Atsushi Iwama, Atsushi Kaneda, Shigehiro A Kawashima, Motomu Kanai

Affiliations

  • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
  • Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
  • Health and Disease Omics Center, Chiba University, Chuo-ku, Chiba, Japan.
  • Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
  • Institute for Quantitative Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
  • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
  • Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

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.

MeSH

Cells, Biological Science Disciplines, Neoplasms, Chromatin, Leukemia, Histones, Epigenome