The successful development and ongoing functioning of complex organisms depends on the faithful execution of the genetic code. A critical step in this process is the correct spatial and temporal expression of genes. The highly orchestrated transcription of genes is controlled primarily by cis-regulatory elements: promoters, enhancers, and insulators. The medical importance of this key biological process can be seen by the frequency with which mutations and inherited variants that alter cis-regulatory elements lead to monogenic and complex diseases and cancer. Here, we provide an overview of the methods available to characterize and perturb gene regulatory circuits. We then highlight mechanisms through which regulatory rewiring contributes to disease, and conclude with a perspective on how our understanding of gene regulation can be used to improve human health. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 23 is October 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Annu Rev Genomics Hum Genet