Genome–lamina interactions are established de novo in the early mouse embryo

In mammals, the emergence of totipotency after fertilization involves extensive rearrangements of the spatial positioning of the genome 1 , 2 . However, the contribution of spatial genome organization to the regulation of developmental programs is unclear 3 . Here we generate high-resolution maps of genomic interactions with the nuclear lamina (a filamentous meshwork that lines the inner nuclear membrane) in mouse pre-implantation embryos. We reveal that nuclear organization is not inherited from the maternal germline but is instead established de novo shortly after fertilization. The two parental genomes establish lamina-associated domains (LADs) 4 with different features that converge after the 8-cell stage. We find that the mechanism of LAD establishment is unrelated to DNA replication. Instead, we show that paternal LAD formation in zygotes is prevented by ectopic expression of Kdm5b , which suggests that LAD establishment may be dependent on remodelling of H3K4 methylation. Our data suggest a step-wise assembly model whereby early LAD formation precedes consolidation of topologically associating domains. Spatial genome organization into lamina-associated domains is first established in the mouse zygote immediately after fertilization without inheritance from the maternal germline—with the paternal and maternal pronucleus exhibiting different organization, which subsequently converges prior to implantation of the embryo.