The Murine Endogenous Retroviral Element (MuERV-L/MERVL) family of transposable elements drives the 3D reorganisation of the genome in the early mouse embryo.
Transposable elements are abundant genetic components of eukaryotic genomes with important regulatory features affecting transcription, splicing, and recombination, among others. Here we demonstrate that the Murine Endogenous Retroviral Element (MuERV-L/MERVL) family of transposable elements drives the 3D reorganisation of the genome in the early mouse embryo. By generating Hi-C data in 2-cell-like cells, we show that MERLV elements promote the formation of insulating domain boundaries through-out the genome in vivo and in vitro. The formation of these boundaries is coupled to the upregulation of directional transcription from MERVL, which results in the activation of a subset of the gene expression programme of the 2-cell stage embryo. Domain boundaries in the 2-cell stage embryo are transient and can be remodelled without undergoing cell division. Remarkably, we find extensive inter-strain MERVL variation, suggesting multiple non-overlapping rounds of recent genome invasion and a high regulatory plasticity of genome organisation. Our results demonstrate that MERVL drive chromatin organisation during early embryonic development shedding light into how nuclear organisation emerges during zygotic genome activation in mammals.