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 factors, such as active forms of Notch, can directly stimulate by activating enhancers, the effect oncogenic subversion on 3-dimensional (3D) organization cancer genome is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast and B-cell lymphoma, we show that far beyond well-characterized role Notch an activator regulates its direct genes through establishing new long-range regulatory interactions. Moreover, a large fraction Notch-promoted highly interacting enhancer promoter spatial clusters, termed ``3D cliques99. Loss- gain-of-function experiments preferentially targets hyperconnected 3D cliques expression crucial proto-oncogenes. Our observations suggest hijacking factors dysregulate widespread effects genomes.