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High-resolution Hi-C reveals increased chromatin looping with senescence associated with hypomethylation and retrotransposon derepression [RNA-seq]

GSE268487 Homo sapiens Expression profiling by high throughput sequencing 9 samples Submitted 2025/07/31 Platform GPL16791
Summary
This study presents the highest-resolution chromatin map of cellular senescence to date, shedding light on how genomic architecture is altered with this damaging phenotype. Senescence, a driver of aging, is a pro-inflammatory state of proliferative arrest caused by DNA damage; it is associated with epigenetic changes, including those to chromatin organization. We created ~3kb Hi-C contact maps of proliferating, quiescent, and replicative senescent lung fibroblasts, and also compared these to oncogene-induced senescence. Our findings confirm a loss of heterochromatin, with a shift towards the A compartment and A subcompartments. We establish a novel loop analysis framework, revealing the ~six times more unique loops with senescence, which lose methylation at their anchors. Additionally, we present a custom long-read reference genome highlighting structural changes supporting retrotransposon derepression, particularly at a defined ‘hotspot’. These architectural changes contribute to senescence, as they promote cell cycle arrest and inflammation, as well as epigenetic drift.
Published in
Senescence-Associated Chromatin Rewiring Promotes Inflammation and Transposable Element Activation
Dalgarno A, Evans SA, Kelsey MMG et al. · bioRxiv : the preprint server for biology 2025 · PMID 40666907 · doi:10.1101/2025.06.11.659151
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Direct links to NCBI, no account and no request form: the whole study as GSE268487_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 PRJNA1117443 and SRA study SRP510290. Searching any of these in the dataset finder brings you back here.

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