Résumé
Mammalian development begins with the formation of a totipotent embryo; however, the molecular mechanisms underlying the acquisition of totipotency are largely unknown. In this study by Peters and colleagues, the authors investigate the role of mammalian Polycomb proteins in the initiation of mammalian development. By using conditional gene disruption approaches, the authors demonstrate that embryos deficient for maternal and zygotic gene function of Ring1 and Rnf2, two core components of the PRC1 complex, arrest their development at the two-cell stage. In addition, the authors show that Ring1 and Rnf2 define cytoplasmic and chromosomal maternal contributions during oogenesis and that this is essential for proper initiation of embryonic development. Thus, this study provides novel insights into the role of Polycomb proteins in the female germline and early mammalian development. In mammals, totipotent embryos are formed by fusion of highly differentiated gametes. Acquisition of totipotency concurs with chromatin remodeling of parental genomes, changes in the maternal transcriptome and proteome, and zygotic genome activation (ZGA). The inefficiency of reprogramming somatic nuclei in reproductive cloning suggests that intergenerational inheritance of germline chromatin contributes to developmental proficiency after natural conception. Here we show that Ring1 and Rnf2, components of Polycomb-repressive complex 1 (PRC1), serve redundant transcriptional functions during oogenesis that are essential for proper ZGA, replication and cell cycle progression in early embryos, and development beyond the two-cell stage. Exchange of chromosomes between control and Ring1/Rnf2-deficient metaphase II oocytes reveal cytoplasmic and chromosome-based contributions by PRC1 to embryonic development. Our results strongly support a model in which Polycomb acts in the female germline to establish developmental competence for the following generation by silencing differentiation-inducing genes and defining appropriate chromatin states.