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DNA topoisomerase II promotes N6-adenosine mRNA methylation [ChIPseq]

GSE281645 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 4 samples Submitted 2025/09/17 Platform GPL18573
Summary
Topoisomerase II (TOP2) is an enzyme that regulates of DNA topology, primarily by removing DNA supercoiling. This function is crucial during transcription, as the movement of RNA polymerase II (RNAPII) generates torsional stress. However, the specific role of TOP2 in the regulation of gene expression remains to be fully elucidated, as both TOP2 inhibitors and poisons have been shown to upregulate specific genes. In this study, we show that TOP2 poisoning negatively affects transcription elongation of genes repressed at the level of promoter-proximal pausing. Importantly, this effect is counteracted by a defective mRNA N6-adenosine methylation (m6A) which results in altered mRNA turnover and pre-mRNA splicing. We propose that TOP2 serves a dual function, supporting the maintenance of basal transcription elongation while simultaneously promoting m6A modification in pre-mRNAs to reduce the overall gene expression output.
Published in
DNA topoisomerase II promotes N(6)-adenosine mRNA methylation
Megías-Fernández C, Delgado-Sainz I, León-Halcón A et al. · Cell reports 2025 · PMID 41171762 · doi:10.1016/j.celrep.2025.116468
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Direct links to NCBI, no account and no request form: the whole study as GSE281645_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 4 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1185147 and SRA study SRP544651. Searching any of these in the dataset finder brings you back here.

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