Super-enhancer

The structures of a typical enhancer compared to a super-enhancer.

Cell differentiation in multicellular organisms with different cell types is determined, in each cell type, by the expression of genes under the regulatory control of typical enhancers and super-enhancers.

A typical enhancer(TE), as illustrated in the top panel of the Figure, is a several hundred base pair region of DNA[1][2] that can bind transcription factors to sequence motifs on the enhancer. The typical enhancer can come in proximity to its target gene through a large chromosome loop. A Mediator a complex (consisting of about 26 proteins in an interacting structure) communicates regulatory signals from the enhancer-located DNA-bound transcription factors to the promoter of a gene, regulating RNA transcription of the target gene.

A super-enhancer, illustrated in the lower panel of the Figure, is a region of the mammalian genome comprising multiple typical enhancers that is collectively bound by an array of transcription factor proteins to drive transcription of genes involved in cell identity,[3][4][5] or of genes involved in cancer.[6] Because super-enhancers frequently occur near genes important for controlling and defining cell identity, they may be used to quickly identify key nodes regulating cell identity.[5][7] Super-enhancers are also central to mediating dysregulation of signaling pathways and promoting cancer cell growth.[6][8] Super-enhancers differ from typical enhancers, however, in that they are strongly dependent on additional specialized proteins that create and maintain their formation, including BRD4 (shown in the lower panel of Figure) and co-factors including p300.[9]

Enhancers have several quantifiable traits that have a range of values, and these traits are generally elevated at super-enhancers. Super-enhancers are bound by higher levels of transcription-regulating proteins and are associated with genes that are more highly expressed.[3][10][11][12] Expression of genes associated with super-enhancers is particularly sensitive to perturbations, which may facilitate cell state transitions or explain sensitivity of super-enhancer—associated genes to small molecules that target transcription.[3][10][11][13][14]

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  5. ^ a b Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-André V, Sigova AA, Hoke HA, Young RA (November 2013). "Super-enhancers in the control of cell identity and disease". Cell. 155 (4): 934–47. doi:10.1016/j.cell.2013.09.053. PMC 3841062. PMID 24119843.
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