Chromatin dynamics underlying the precise regeneration of a vertebrate limb – Epigenetic regulation and cellular memory

Wound healing, tissue regeneration, and organ regrowth are all regeneration phenomena observed in vertebrates after an injury. However, the ability to regenerate differs greatly among species. Mammals can undergo wound healing and tissue regeneration, but cannot regenerate an organ; for example, they cannot regrow an amputated limb. In contrast, amphibians and fish have much higher capabilities for organ-level regeneration. In addition to medical studies and those in conventional mammalian models such as mice, studies in amphibians and fish have revealed essential factors for and mechanisms of regeneration, including the regrowth of a limb, tail, or fin. However, the molecular nature of the cellular memory needed to precisely generate a new appendage from an amputation site is not fully understood. Recent reports have indicated that organ regeneration is closely related to epigenetic regulation. For example, the methylation status of genomic DNA is related to the expression of regeneration-related genes, and histone-modification enzymes are required to control the chromatin dynamics for regeneration. A proposed mechanism of cellular memory involving an inheritable system of epigenetic modification led us to hypothesize that epigenetic regulation forms the basis for cellular memory in organ regeneration. Here we summarize the current understanding of the role of epigenetic regulation in organ regeneration and discuss the relationship between organ regeneration and epigenetic memory.