{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE344nnn/GSE344392/"]},"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=GSE344392"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"PRCC-TFE3 Forms Proline-dependent Condensates and Reprograms Chromatin for tRCC Oncogenic Transcription [CUT&RUN]","description":"Translocation renal cell carcinoma (tRCC) is an aggressive malignancy driven by MiT/TFE family transcription factor rearrangements, most notably TFE3 fusions. Among these, the PRCC::TFE3 fusion is a prominent oncogenic driver, yet the molecular mechanisms governing its transcriptional and tumorigenic activities remain poorly defined. Here, we demonstrate that PRCC::TFE3 forms dynamic, transcriptionally active nuclear condensates that are critical for its oncogenic function. We identify a proline-rich region within the PRCC fusion partner as the essential determinant of condensate formation. Disruption of this proline-rich region (PRW) abolishes condensate assembly, reverses fusion-driven chromatin accessibility and transcriptional reprogramming, and suppresses proliferative, migratory, and invasive phenotypes in patient-derived tRCC cell lines. Integrative RNA-seq, ATAC-seq, and CUT&RUN analyses reveal that PRCC::TFE3 condensates function as epigenetic regulatory hubs, coordinating extensive chromatin remodeling and recruitment of transcription factor networks—including TEAD-associated pathways—to amplify oncogenic programs. Furthermore, we identify HS3ST2 and ABCB5 as novel, condensate-dependent target genes and validate them as critical mediators of tRCC progression. Our findings establish PRCC::TFE3-mediated condensate formation as a fundamental mechanism of tRCC pathogenesis and highlight condensate-dependent transcriptional networks as potential therapeutic vulnerabilities in this clinically challenging disease.","dates":{"publication":"2026/08/20"},"accession":"GSE344392","cross_references":{"GSM":["GSM9978333","GSM9978332","GSM9978335","GSM9978334","GSM9978337","GSM9978326","GSM9978336","GSM9978339","GSM9978328","GSM9978338","GSM9978327","GSM9978329","GSM9978340","GSM9978342","GSM9978331","GSM9978330","GSM9978341"],"GPL":["34284"],"GSE":["344392"],"taxon":["Homo sapiens"]}}