Genomics

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


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE259437 | GEO | 2024/12/04

REPOSITORIES: GEO

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