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Mesoscale proximity labeling at chromatin to study small molecule mechanism of action [CUTandTag_2]

GSE304410 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 9 samples Submitted 2025/08/08 Platform GPL30173
Summary
Proximity labeling traditionally identifies interactomes of a single protein or RNA, though this approach limits mechanistic understanding of biomolecules functioning within complex systems. Here, we demonstrate a strategy for deciphering ligand-induced changes to global biomolecular interactions by enabling proximity labelling at the mesoscale, across an entire cellular system. By inserting nanoscale proximity labelling catalysts throughout chromatin, this system, MesoMap, provided new insights into how HDAC inhibitors regulate gene expression. Furthermore, it revealed that the orphaned drug candidate, SR-1815, regulates disease-linked Syngap1 gene expression through direct inhibition of kinases implicated in both neurological disorders and cancer. Through precise mapping of global chromatin mobility, MesoMap promotes insights into how drug-like chemical probes induce transcriptional dynamics within healthy and disease-associated cellular states.
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Direct links to NCBI, no account and no request form: the whole study as GSE304410_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 9 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1301263 and SRA study SRP606419. Searching any of these in the dataset finder brings you back here.

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