Regeneration enhancers: a field in development

The ability to regenerate tissues and organs following damage is not equally distributed across metazoans, and even highly related species can vary considerably in their regenerative capacity. Studies of animals with high regenerative potential have shown that factors expressed during normal development are often reactivated upon damage and required for successful regeneration. As such, regenerative potential may not be dictated by the presence or absence of the necessary genes, but whether such genes are appropriately activated following injury. The identification of damage-responsive enhancers that regulate regenerative gene expression in multiple species and tissues provides possible mechanistic insight into this phenomenon. Enhancers that are reused from developmental programs, and those that are potentially unique to regeneration, have been characterized individually and at a genome-wide scale. A better understanding of the regulatory events that, direct and in some cases limit, regenerative capacity is an important step in developing new methods to manipulate and augment regeneration, particularly in tissues that do not have this ability, including those of humans.