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We identified a specific enhancer-associated LINC01116 (named HOXDeRNA), which targeted activation transformed human astrocytes into glioma-like cells. Using a combination of RNA-Seq, ChIRP-Seq, and ChIP-Seq, we defined the transcriptomic and epigenetic changes underlying the transformation. We demonstrate that HOXDeRNA binds in trans to the promoters of 44 glioma-specific transcription factors distributed throughout the genome and derepresses them by removing the Polycomb 2 complex. This process is mediated by the RNA G-quadruplex structure of HOXDeRNA. Moreover, HOXDeRNA-induced astrocyte transformation is accompanied by the activation of glioma-specific super-enhancers enriched for binding sites of glioma master transcription factors SOX2 and OLIG2, and multiple oncogenes such as EGFR, PDGFR, BRAF, and miR-21. Our results help reconstruct the sequence of events underlying the process of astrocyte transformation and suggest a driving role of HOXDeRNA eRNA in gliomagenesis. Overall design: mRNA-Seq was performed on fetal human astrocytes, Immortalized dCas9 expressing astrocytes (NHA) transduced with sgRNA non-targeting control and custom-made Edit-R CRISPRa human HOXDeRNA lentiviral sgRNAs"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Genome-wide activation of a glioma cancerous transcription program and super-enhancers by a single enhancer HOXDeRNA [RNA-seq]","description":"Genome-wide activation of a glioma cancerous transcription program and super-enhancers by a single enhancer HOXDeRNA [RNA-seq]","dates":{"last_updated":"2025-09-24","first_public":"2023-04-05"},"accession":"PRJNA947105","cross_references":{"GEO":["GSE227802"],"taxon":["9606"],"PubMed":["37425921"]}}