Early embryogenesis involves a switch from parentally repressive chromosomal domains to de novo TADs

Paternal and maternal epigenomes undergo dramatic changes after fertilization. How this relates to the 3D reorganisation of the parental genomes and their transcription patterns during early development remains unclear. Here we track structural dynamics during early mouse development using allele-specific single cell HiC integrated with transcriptome and chromatin changes, to combine parental features with early gene expression including during imprinted X-chromosome inactivation. We uncover a marked structural asymmetry following fertilization, with mostly maternal-specific domains of interaction that coincide with polycomb H3K27me3 domains. They form local repressive compartments and result in parentally-biased gene expression, including transient imprinting loci such as the X-inactivation center. These asymmetric domains later resolve into classical active and inactive compartments. Topologically associated domains are also established progressively, in a non parental specific manner and are associated with active chromatin. They are lost when gene expression is not maintained on the paternal X. Our study reveals unprecedented dynamics in parental specific 3D genome organization and gene expression during early development. Overall design: We performed single cell HiC in mouse embryos from hybrid crosses at different stages