Superenhancerdriven

Superenhancerdriven, more commonly written as super-enhancer-driven, is a designation used in genomics to describe gene expression programs, cell states, or disease phenotypes that are mainly governed by super-enhancers. Super-enhancers are large, densely clustered assemblies of regulatory elements that drive high transcription of genes essential for cell identity. They are characterized by exceptionally high occupancy of transcriptional coactivators such as the Mediator complex, BRD4, and RNA polymerase II, and by expansive regions enriched for the histone modification H3K27ac.

Because they regulate key identity genes, super-enhancer-driven expression is typically robust and particularly sensitive to perturbations in the transcriptional machinery. In practice, researchers identify super-enhancers with genome-wide assays like ChIP-seq for H3K27ac or Mediator, followed by computational ranking (e.g., ROSE) to distinguish broad, high-activity regions from typical enhancers.

Biologically, many normal developmental programs and cell-type–specific states are associated with super-enhancer–driven regulation. In cancer and other diseases, oncogenes or pathogenic networks are frequently under super-enhancer control, contributing to tumor dependency on these elements. Therapeutically, BRD4 and other coactivators at super-enhancers are explored as drug targets; BET inhibitors can preferentially downregulate super-enhancer–driven transcription.

Terminology note: while the common form is "super-enhancer-driven," some uses join the term as "superenhancerdriven." The concept refers to regulation primarily by super-enhancers. Ongoing debate focuses on whether super-enhancers constitute a distinct class of enhancers or a continuum, and on the functional validation required to establish causality.