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

ABSTRACT: Chromatin loops enable transcription-factor-bound distal enhancers to interact with their target promoters to regulate transcriptional programs. Although developmental transcription factors such as active forms of Notch can directly stimulate transcription by activating enhancers, the effect of their oncogenic subversion on the 3D organization of cancer genomes is largely undetermined. By mapping chromatin looping genome-wide in Notch-dependent triple-negative breast cancer and B cell lymphoma, we show that beyond the well-characterized role of Notch as an activator of distal enhancers, Notch regulates its direct target genes by instructing enhancer repositioning. Moreover, a large fraction of Notch-instructed regulatory loops form highly interacting enhancer and promoter spatial clusters

SUBMITTER: Petrovic J 

PROVIDER: S-EPMC6485942 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature