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Rapid PTEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy [ATAC-Seq]

GSE227792 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2024/04/12 Platform GPL24676
Summary
Using a combination of ChIP-, ATAC-, RNA-seq, and CUT&RUN in model systems of diffuse intrinsic pontine glioma and other pediatric high-grade gliomas, we observe a rapid genome-wide reorganization of active chromatin within hours of exposure to therapeutic ionizing radiation. This redistribution facilitates PTEFb-mediated pause-release of Pol II to drive nascent transcriptional induction of canonical DNA damage response programs. Concurrent inhibition of PTEFb imparts a transcription elongation defect, disrupting this chromatin reorganization and blunting transcriptional induction. Functionally, concurrent PTEFb inhibition abrogates key adaptive programs such as DNA damage repair and cell cycle regulation. This combination demonstrates a potent, synergistic therapeutic potential agnostic of glioma subtype, leading to a marked induction of tumor cell apoptosis and prolongation of xenograft survival.
Published in
Rapid P-TEFb-dependent transcriptional reorganization underpins the glioma adaptive response to radiotherapy
Walker FM, Sobral LM, Danis E et al. · Nature communications 2024 · PMID 38816355 · doi:10.1038/s41467-024-48214-3
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Also filed as BioProject PRJNA947087 and SRA study SRP434383. Searching any of these in the dataset finder brings you back here.

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