Sequential chromatin reprogramming at single-nucleus resolution defines the onset of mammalian development

ABSTRACT: Mammalian development begins with extensive reprogramming after fertilization, yet how parental chromatin is remodeled within individual pronuclei remains poorly resolved. We developed ultra-low-input single-nucleus ATAC-seq (ULI-snATAC-seq) to profile maternal and paternal pronuclei independently and generated a mouse single-nucleus chromatin-accessibility atlas of 3,185 nuclei spanning oocyte to blastocyst. Chromatin remodeling proceeded through sequential temporal modules, from transient zygotic genome activation (ZGA)-associated states to sustained and lineage-associated states, with substantial convergence of parental chromatin states by the early 2-cell stage. ZGA was accompanied by a genome-wide increase in chromatin accessibility and enrichment of candidate motifs corresponding to 141 transcription factors (TFs), including Obox, Otx2, Nr5a2, Dux and Zscan4. Analysis at single-copy resolution further resolved individual B1 elements that were accessible during development and linked to ZGA-associated genes, with enrichment of motifs for ZGA-associated TFs. These data provide a pronucleus-resolved view of parental chromatin reprogramming and nominate B1-associated sequences as candidate cis-regulatory features of ZGA.

ORGANISM(S): Mus musculus

PROVIDER: GSE282209 | GEO | 2026/01/13

REPOSITORIES: GEO