Chromatin Accessibility Landscape of Mouse Preimplantation Embryos Analyzed by Single-cell NanoATAC-seq2

In mammals, fertilized eggs undergo genome-wide epigenetic reprogramming to generate the organism and extra-embryonic tissues. However, our understanding of epigenetic dynamics during preimplantation development at single-cell resolution remains incomplete. To address this, we developed scNanoATAC-seq2, a single-cell chromatin accessibility assay using long-read sequencing for scarce samples. We present a detailed chromatin accessibility landscape of mouse preimplantation development, revealing distinct chromatin signatures in the epiblast, primitive endoderm, and trophectoderm during lineage segregation. Differences between zygotes and 2-cell embryos highlight reprogramming in chromatin accessibility during the maternal-to-zygotic transition. Single-cell long-read sequencing enables in-depth analysis of chromatin accessibility in non-canonical imprinting, X chromosome inactivation, and low-mappability genomic regions such as repetitive elements and paralogs. This analysis provides novel insights into chromatin dynamics in preimplantation embryos.