Super-enhancer-mediated core regulatory circuitry in human cancer.

Super-enhancers (SEs) are congregated enhancer clusters with high level of loading of transcription factors (TFs), cofactors and epigenetic modifications. Through direct co-occupancy at their own SEs as well as each other's, a small set of so called "master" TFs form interconnected core regulatory circuitry (CRCs) to orchestrate transcriptional programs in both normal and malignant cells. These master TFs can be predicted mathematically using epigenomic methods. In this Review, we summarize the identification of SEs and CRCs in cancer cells, the mechanisms by which master TFs and SEs cooperatively regulate cancer-type-specific expression programs, and the cancer-type- and subtype-specificity of CRC and the significance in cancer biology.