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Epigenomic manipulation reveals the relationship between locus specific chromatin dynamics and gene expression [ChIP-seq]

GSE282760 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 36 samples Submitted 2025/11/18 Platform GPL30173
Summary
Dysregulation of epigenetic processes leads to a plethora of abnormalities including disease states such as cancer. Therapies focused on epigenetic modulation alter gene expression to correct dysfunction, though the mechanisms and perpetuation of these states is unknown. Here, we use integrated epigenomics and three-dimensional chromatin structure-function analyses after acute histone deacetylase inhibitor cancer drug treatment (suberoylanilide hydroxamic acid in lung cancer cells). Treatment induced substantial (13%) genomic rearrangement that rebounds despite persistent gene expression changes and spreading of acetylation. The chromatin functional landscape (accessibility, active transcription modification, and gene expression) is controlled and locus-specific, while chromatin contacts are globally altered resulting in a moderate weakening of topologically associating domains. Chromatin states are more dynamic at transcriptionally active loci while genes with reduced expression are epigenetically stable suggesting chromatin architectural turnover and nucleosome remodeling is locus-specific and underlies the bidirectional expression changes. Thus, local 3D chromatin and genome structural dynamics is integral for loci regulation in response to epigenomic perturbation. The partial persistence of these altered features may have larger implications for efficacy of epigenetic drugs in amelioration of disease states.
Published in
Disruption of histone acetylation homeostasis reveals multilayered chromatin regulation for transcriptional resiliency
Venu V, Small EM, Roth C et al. · Epigenetics & chromatin 2025 · PMID 41044756 · doi:10.1186/s13072-025-00631-4
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Direct links to NCBI, no account and no request form: the whole study as GSE282760_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 36 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1135966 and SRA study SRP519925. Searching any of these in the dataset finder brings you back here.

Study design
12 conditions, mostly in triplicate
24hr Control H3ac ChIP-seq ×3 24hr SAHA Treated H3ac ChIP-seq ×3 48hr Control H3ac ChIP-seq ×3 48hr SAHA Treated H3ac ChIP-seq ×3 24hr Control H3K27ac ChIP-seq ×3 24hr SAHA Treated H3K27ac ChIP-seq ×3 48hr Control H3K27ac ChIP-seq ×3 48hr SAHA Treated H3K27ac ChIP-seq ×3 +4 more

Supports a case/control comparison: 18 samples read as cases, 18 as controls.

12 replicated groups read from 36 sample titles; they account for 36 of them. Check it against the sample list below before relying on it.

Samples in this study
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