Regeneration enhancers: A clue to reactivation of developmental genes

During tissue and organ regeneration, cells initially detect damage and then alter nuclear transcription in favor of tissue/organ reconstruction. Until recently, studies of tissue regeneration have focused on the identification of relevant genes. These studies show that many developmental genes are reused during regeneration. Concurrently, comparative genomics studies have shown that the total number of genes does not vastly differ among vertebrate taxa. Moreover, functional analyses of developmental genes using various knockout/knockdown techniques demonstrated that the functions of these genes are conserved among vertebrates. Despite these data, the ability to regenerate damaged body parts varies widely between animals. Thus, it is important to determine how regenerative transcriptional programs are triggered and why animals with low regenerative potential fail to express developmental genes after injury. Recently, we discovered relevant enhancers and named them regeneration signal-response enhancers (RSREs) after identifying their activation mechanisms in a Xenopus laevis transgenic system. In this review, we summarize recent studies of injury/regeneration-associated enhancers and then discuss their mechanisms of activation.