Epigenetic mechanisms in early mammalian development

After fertilisation, a new developmental programme starts, whereby a single cell, the one-cell embryo or zygote, will form an entire new organism. The period that follows fertilisation is characterised by major changes in cellular plasticity and potency. Coinciding with these changes in cellular potency, massive alterations occur in the nucleus, with major transcriptional, epigenetic and architectural remodelling, as well as the establishment of the DNA replication landscape. In particular, replication timing is a major epigenetic fingerprint, which is linked to nuclear organisation. Understanding how nuclear organisation and the replication timing programme are first established at the beginning of development is essential to decipher how the first epigenetic regulatory layers are set in place during development. I will discuss recent advances in this area, which have informed us on how the early embryo controls its DNA-based processes, the regulation of DNA replication and its molecular interdependencies with epigenetic regulation and nuclear organisation.