{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314776/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314776"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer [ChIP-Seq]","description":"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.","dates":{"publication":"2026/06/15"},"accession":"GSE314776","cross_references":{"GSM":["GSM9410350","GSM9410330","GSM9410341","GSM9410340","GSM9410351","GSM9410332","GSM9410343","GSM9410342","GSM9410331","GSM9806579","GSM9410345","GSM9410334","GSM9410333","GSM9410344","GSM9410347","GSM9410335","GSM9410346","GSM9410349","GSM9410348","GSM9410329","GSM9410328","GSM9806582","GSM9806581","GSM9806580"],"GPL":["34284","24676"],"GSE":["314776"],"taxon":["Homo sapiens"]}}