The impact of retrotransposons on zygotic genome activation and the chromatin landscape of early embryos

In mammals, fertilization is followed by extensive reprogramming and reorganization of the chromatin accompanying the transcriptional activation of the embryo. This reprogramming results in blastomeres with the ability to give rise to all cell types and a complete organism, including extra-embryonic tissues, and is known as totipotency. Transcriptional activation occurs in a process known as zygotic genome activation (ZGA) and is tightly linked to the expression of transposable elements, including endogenous retroviruses (ERVs) such as endogenous retrovirus with leucine tRNA primer (ERVL). Recent studies discovered the importance of ERVs in this process, yet the race to decipher the network surrounding these elements is still ongoing, and the molecular mechanism behind their involvement remains a mystery. Amid a recent surge of studies reporting the discovery of various factors and pathways involved in the regulation of ERVs, this review provides an overview of the knowns and unknowns in the field, with a particular emphasis on the chromatin landscape and how ERVs shape preimplantation development in mammals. In so doing, we highlight recent discoveries that have advanced our understanding of how these elements are involved in transforming the quiescent zygote into the most powerful cell type in mammals.