Superenhancers create hotspots of DNA fragility and mutations by intensifying transcription-associated breakage and repair.

Cell identity genes that exhibit complex regulation are marked by super-enhancer (SE) architecture. Assessment of SEs in natural killer (NK) cells ide…

MYOD is an E-box sequence-specific basic Helix-Loop-Helix (bHLH) transcriptional activator that, when expressed in non-muscle cells, induces nuclear reprogramming toward skeletal myogenesis by promoti...

Chronic allograft rejection is mainly mediated by indirect recognition. Dendritic cells (DCs), as the major antigen-presenting cells in indirect recognition, exhibit an enhanced antigen-presenting abi...

Superenhancers create hotspots of DNA fragility and mutations by intensifying transcription-associated breakage and repair.

Key PointsIKZF1 and NuRD induce rapid loss of chromatin accessibility and H3K27ac at enhancers and superenhancers to repress target genes.Immediate IKZF1 t

ROSE: RANK ORDERING OF SUPER-ENHANCERS. Contribute to crazyhottommy/ROSE2 development by creating an account on GitHub.

Superenhancers create hotspots of DNA fragility and mutations by intensifying transcription-associated breakage and repair.

Super-enhancers (SEs) are highly enriched clusters of transcriptional regulatory elements within the genome, occupying a central position in tumorigenesis and development. This review aims to synthesize the rapidly expanding body of knowledge on SEs as the central hub of tumor transcriptional regulation.SEs integrate specific transcription factors, dynamic epigenetic modifications (such as H3K27ac), and restructure the three-dimensional spatial architecture of the genome to aberrantly drive the expression of proto-oncogenes and cell identity-related genes. This activity sustains the malignant phenotype, stem cell properties, metabolic reprogramming, and therapy resistance of tumor cells. Their functions involve emerging physical mechanisms such as phase separation forming transcriptional condensates and long-range chromatin looping. The activity of SEs exhibits high tumor-type and tissue specificity. They are activated through unique mechanisms in different cancers, becoming key nodes of “transcriptional addiction” in tumor cells. This characteristic also makes them highly promising therapeutic targets. Inhibitors targeting core SE components (such as the BET protein BRD4 and transcriptional kinases CDK7/9), epigenetic drugs, and strategies aimed at disrupting their phase-separated condensates have shown selective efficacy in various preclinical tumor models. In conclusion, SEs serve as pivotal hubs of transcriptional addiction in cancer by integrating diverse molecular mechanisms to drive oncogenic programs, and their specific components present promising therapeutic targets; future advances in multi-omics and precision strategies will be key to translating these findings into clinical applications.