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Cancer epigenome intervention by in-cell chemical catalysis for histone modification (RNA-seq)

GSE259436 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/12/04 Platform GPL24676
Summary
Chemical modification of histones dynamically regulates gene transcription and is closely related to disease pathogenesis including cancer. Targeting epigenome is thus a promising strategy for cancer chemotherapy. Here we report a novel histone acetylation catalyst BAHA-LANA-PEG-CPP44 that can intervene into cancer epigenome. The catalyst selectively entered leukemia cells, bound to chromatin, and acetylated endogenous histones, especially at H2BK120, in a HAT-independent manner. The catalytic histone acetylation attenuated chromatin binding of negative elongation factor E (NELFE), an RNA polymerase II pausing factor, and reprogramed transcription profile in leukemia cells. The in-cell chemical catalysis retarded proliferation of leukemia cells and reduced their tumorigenic potential in mice. Our catalyst is orthogonal to cancer epigenetic drugs targeting histone-modifying enzymes and may lead to a novel anti-cancer strategy.
Published in
Chemical catalyst manipulating cancer epigenome and transcription
Yamanashi Y, Takamaru S, Okabe A et al. · Nature communications 2025 · PMID 39856033 · doi:10.1038/s41467-025-56204-2
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Also filed as BioProject PRJNA1081773 and SRA study SRP492255. Searching any of these in the dataset finder brings you back here.

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