Oncogenic Notch Promotes Long-Range Regulatory Interactions within Hyperconnected 3D Cliques

摘要: Chromatin loops enable transcription-factor-bound distal enhancers to interact with their target promoters regulate transcriptional programs. Although developmental transcription factors such as active forms of Notch can directly stimulate by activating enhancers, the effect oncogenic subversion on 3D organization cancer genomes is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast and B cell lymphoma, we show that beyond well-characterized role an activator regulates its direct genes instructing enhancer repositioning. Moreover, a large fraction Notch-instructed regulatory form highly interacting promoter spatial clusters termed "3D cliques." Loss- gain-of-function experiments preferentially targets hyperconnected cliques expression crucial proto-oncogenes. Our observations suggest hijacking dysregulate through widespread effects genomes.