The landscape of accessible chromatin in mammalian preimplantation embryos

In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis -regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis -regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis -regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development. An improved ATAC-seq approach is used to describe a genome-wide view of accessible chromatin and cis -regulatory elements in mouse preimplantation embryos, allowing construction of a regulatory network of early development that helps to identify key modulators of lineage specification. The chromatin landscape in early embryos Early animal embryos undergo dramatic reprogramming and chromatin remodelling during the conversion of terminally differentiated gametes to totipotent cells. Wei Xie and colleagues use an ATAC-seq approach to describe a genome-wide view of accessible chromatin and cis -regulatory elements in mouse preimplantation embryos. Despite the globally asymmetric patterns of DNA methylation and certain histone modifications on the maternal and paternal genomes in early embryos, they find a comparably accessible chromatin landscape on the two parental alle