Enhancer and superenhancer regulation and its disruption in cancer

Enhancers are DNA elements that promote transcription of distal genes and have a key role in regulating gene expression in metazoans. Disruption of proper gene expression can cause overexpression of oncogenes and silencing of tumor suppressors which results in cancer. Thus, dysregulation of enhancer function plays an important role in cancer initiation and progression. A growing body of work reveals that enhancers typically interact with the promoter they regulate and that topological domains constrain enhancer–promoter interactions but that there are also many exceptions to these rules. The discovery that enhancers, and especially superenhancers, support the formation of biomolecular condensates that drive transcription elucidates the requirements for efficient transcription and the biophysical processes that support it. Systematic studies have revealed how genetic, epigenetic, and topologic alterations disrupt enhancer regulation to drive cancer and hold great promise to improve cancer prognosis and therapy.