p53: master of life, death, and the epigenome

Long understood as a bona fide tumor suppressor that safeguards the integrity of the genome via regulating numerous cellular outcomes, p53 may also exert its decisive and versatile functions by controlling DNA methylation. In this issue of Genes & Development, Tovy and colleagues (pp. 959-972) report that, in naive mouse embryonic stem cells (ESCs), p53 controls DNA methylation homeostasis by regulating the expression of key counteracting components of the DNA methylation machinery. Their findings indicate that p53 may exert its "guardian of genome" duties at least in part via safeguarding the epigenome of ESCs.