GEO series
Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer [ChIP-Seq]
GSE314776
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
24 samples
Submitted 2026/06/15
Platform GPL34284Platform GPL24676
Summary
Background: The transcription process is controlled by non-coding regulatory elements, more than 70% of which are putative enhancers. These enhancers comprise over 600,000 regions and are marked by histone modifications. However, the mechanisms by which altered enhancers in cancer cooperate within the three-dimensional chromatin architecture to drive oncogenic programs remain poorly understood. Results: By integrating 201 H3K27ac ChIP seq datasets from prostate, we identify 3,216 high confidence prostate cancer-specific putative enhancers. Ultra high resolution chromatin interaction profiling by Region Capture Micro-C at a representative chr6q24.1 locus reveals that these enhancers form cancer specific, highly nested interactions with promoters that coalesce into a multi connected hub absent in normal prostate cells. CRISPR/Cas9 perturbations of these enhancers, examined one by one, distinguish enhancer classes within the hub. Deletion of a central enhancer collapses hub-wide enhancer activities and architecture, leading to the downregulation of target genes, impaired proliferation, and reduced clonogenic growth. In contrast, deletion of a redundant enhancer results in minimal transcriptional changes, as neighboring enhancers rescue cancer signaling through compensatory architectural rewiring that strengthens alternative enhancer-promoter interactions. We also observe that FOXA1, a pioneer transcription factor activated in prostate cancer, directly binds to these enhancers and regulates distinct enhancer classes, leading to varying degrees of chromatin accessibility and gene expression changes. Conclusions: These findings suggest that enhancers function in a coordinated manner, forming multi-connected cancer-specific chromatin interaction hubs, with distinct enhancer classes contributing differently to gene regulation. This study advances our ability to modulate gene expression in a cell type-specific manner, opening new avenues for precision therapies.
Published in
Cao H, Wu Z, Ji B et al.
· Genome biology 2026
· PMID 42487124
· doi:10.1186/s13059-026-04178-9
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE314776_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1392579 and SRA study SRP657432. Searching any of these in the dataset finder brings you back here.
Study design
12 conditions, mostly in duplicate
22Rv1_H3K27ac_NTC ×2
22Rv1_H3K27ac_cPCE_del ×2
22Rv1_H3K27ac_rPCE_del ×2
22Rv1_H3K27ac_resPCE_del ×2
22Rv1_CTCF_NTC ×2
22Rv1_CTCF_cPCE_del ×2
22Rv1_FOXA1_NTC ×2
22Rv1_FOXA1_cPCE_del ×2
+4 more
Supports a between-group comparison across 24 samples.
12 replicated groups read from 24 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9410328 22Rv1_H3K27ac_NTC_R1
- GSM9410329 22Rv1_H3K27ac_NTC_R2
- GSM9410330 22Rv1_H3K27ac_cPCE_del_R1
- GSM9410331 22Rv1_H3K27ac_cPCE_del_R2
- GSM9410332 22Rv1_H3K27ac_rPCE_del_R1
- GSM9410333 22Rv1_H3K27ac_rPCE_del_R2
- GSM9410334 22Rv1_H3K27ac_resPCE_del_R1
- GSM9410335 22Rv1_H3K27ac_resPCE_del_R2
- GSM9410340 22Rv1_CTCF_NTC_R1
- GSM9410341 22Rv1_CTCF_NTC_R2
- GSM9410342 22Rv1_CTCF_cPCE_del_R1
- GSM9410343 22Rv1_CTCF_cPCE_del_R2
- GSM9410344 22Rv1_FOXA1_NTC_R1
- GSM9410345 22Rv1_FOXA1_NTC_R2
- GSM9410346 22Rv1_FOXA1_cPCE_del_R1
- GSM9410347 22Rv1_FOXA1_cPCE_del_R2
- GSM9410348 22Rv1_FOXA1_rPCE_del_R1
- GSM9410349 22Rv1_FOXA1_rPCE_del_R2
- GSM9410350 22Rv1_CTCF_rPCE_del_R1
- GSM9410351 22Rv1_CTCF_rPCE_del_R2
- GSM9806579 RC77NE_H3K27ac_R1
- GSM9806580 RC77NE_H3K27ac_R2
- GSM9806581 RC77TE_H3K27ac_R1
- GSM9806582 RC77TE_H3K27ac_R2
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