The interplay between epigenetic changes and the p53 protein in stem cells.

Epigenetic programs regulate the development and maintenance of organisms over a lifetime. These programs are carried out through chemical modifications of DNA and proteins such as histones and transcription factors. These epigenetic modifications are less stable than genetic alterations and even reversible under a variety of circumstances, such as developmental changes, regeneration of tissues, cell divisions, aging, and pathological conditions observed in many cancers. The p53 protein not only enforces the stability of the genome by the prevention of genetic alterations in cells but also plays a role in regulating the epigenetic changes that can occur in cells. The full-length p53 protein is largely inactive in stem cells but, when activated, helps to commit these cells to developmental lineages through a series of epigenetic changes. Just as p53 impacts epigenetic change, the enzyme activities that carry out epigenetic protein modifications act on the p53 protein and its splice variants in stem and progenitor cells to silence or activate its transcriptional activities. Thus, there is a great deal of cross-talk between the p53 protein and epigenetic programs. This review collects the diverse experimental evidence that leads to these conclusions. This in turn permits new ideas and directions for the treatment of cancers, reactivating developmental pathways for tissue regeneration and responses to the impact of aging.