Developmentally programmed epigenome regulates cellular plasticity at the parental-to-zygote transition

During metazoan development, the dramatic potency change from germline to embryos raises an important question regarding how the new life cycle is reset. Here, we report a tightly regulated epigenome landscape change from the parental germline to embryos in C. elegans . The epigenome is enriched with histone H3 in early-stage germ cells but switches to a histone variant H3.3-enriched epigenome in the mature egg. This H3.3-dominant epigenome persists in early-stage embryos until gastrulation, when the epigenome becomes H3 abundant again. We further demonstrate that this developmentally programmed H3 → H3.3 → H3 epigenome landscape change is regulated through differential expression of distinct histone gene clusters and is required for both germline integrity and early embryonic cellular plasticity. Together, this study reveals that a bimodal expression of H3 versus H3.3 is important for epigenetic reprogramming during gametogenesis and embryonic plasticity. One Sentence Summary Developmentally programmed epigenome resets cellular plasticity at the parental-to-zygote transition in C. elegans . ### Competing Interest Statement The authors have declared no competing interest.