H3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase.

ABSTRACT:

Aims

Drivers of the drug tolerant proliferative persister (DTPP) state have not been well investigated. Histone H3 lysine-4 trimethylation (H3K4me3), an active histone mark, might enable slow cycling drug tolerant persisters (DTP) to regain proliferative capacity. This study aimed to determine H3K4me3 transcriptionally active sites identifying a key regulator of DTPPs.

Methods

Deploying a model of adaptive cancer drug tolerance, H3K4me3 ChIP-Seq data of DTPPs guided identification of top transcription factor binding motifs. These suggested involvement of O-linked N-acetylglucosamine transferase (OGT), which was confirmed by metabolomics analysis and biochemical assays. OGT impact on DTPPs and adaptive resistance was explored in vitro and in vivo.

Results

H3K4me3 remod

SUBMITTER: Ravindran Menon D 

PROVIDER: S-EPMC10719180 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature