Enhancer profiling of glioblastoma uncovers core oncogenic dependency and therapeutic opportunity [ChIP-seq]

Here, by mapping H3K27ac deposition, we analyze the active regulatory landscapes across primary GBM biopsies, normal brain tissues, and cell line counterparts. Analysis of differentially regulated enhancers, especially super-enhancers between GBM and normal brain tissues, as well as among GBM samples with matched RNA-sequencing data, uncovered unrecognized layers of oncogenic core transcriptional dependency and inter-tumor heterogeneity. Moreover, we demonstrate the functional relevance of leading candidates of super-enhancer-driven transcriptional factors, long non-coding RNAs, and druggable targets in GBM. Through profiling of transcriptional enhancers, our integrative study provides clinically relevant insights into GBM molecular classification, pathogenesis, and therapeutic innovations. Overall design: ChIP-seq and RNA-seq were performed on GBM samples