Super-enhancer regulatory element (SE)

Super-enhancer regulatory elements are *large genomic regions comprised of clusters of individual enhancers* that are densely occupied by master transcription factors, co-activators (such as Mediator, BRD4, p300), and are marked by high levels of enhancer-associated histone modifications (notably H3K27ac). They function as hubs for the activation of genes essential for cell identity and fate, orchestrating unusually high levels of gene transcription that's highly sensitive to disruptions in the transcriptional machinery. Super-enhancers play critical roles in normal development by maintaining cell identity; in cancer, they are frequently hijacked to drive oncogene overexpression, and consequently, represent a vulnerability for indirect pharmacological targeting by drugs that disrupt their essential co-factors or chromatin state.

Other names

Super-enhancerSESuper-enhancer clusterClustered enhancer regionSuper-enhancer regulatory element

Drugs that affect pathways required for super-enhancer function act by: - Inhibiting co-factors (e.g., BRD4, CDK7, p300/CBP) required for super-enhancer formation and maintenance, which results in selective suppression of super-enhancer–driven gene expression, including oncogenes