Sex-Specific DNA-Replication In The Early Mammalian Embryo

The timing of mammalian DNA replication is crucial for minimizing errors and is influenced locally by genome usage and chromatin states. However, our understanding of replication timing in the unique environment that exists in newly formed mammalian embryos is limited. Here, we performed genome-wide investigations of replication timing in mouse zygotes and 2-cell embryos. We discovered that zygotes lack a conventional replication timing, but a program emerged in 2-cell embryos. Notably, this program differs from embryonic stem cells and shows asynchrony between the parental genomes. We observed late replication of maternal pericentromeric regions and DNA associated with the nuclear lamina in each parental genome, whereas unexpected early replication occurred in regions with histone marks deposited by Polycomb Repressive Complexes on the maternal chromatin. This atypical and asynchronous replication of the two parental genomes may advance our understanding of replication stress in early human embryos and trigger strategies to reduce errors and aneuploidies. ### Competing Interest Statement The authors have declared no competing interest. FOR REVIEWERS (will be deleted from the manuscript upon acceptance): To review GEO accession GSE237400 (First submission data): Reviewer access to the unpublished Repli-seq data for the first submission of this study can be obtained using the link and by entering the token abyfqaiwjrwnrob into the box. The Repli-seq data generated for this publication have been deposited in NCBI’s Gene Expression Omnibus[68][1] and are accessible through GEO Series accession number GSE237400 (). [1]: #ref-68