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Sex-specific DNA-replication in the early mammalian embryo.

Jason Alexander Halliwell | Javier Martin-Gonzalez | Adnan Hashim | John Arne Dahl | Eva R Hoffmann | Mads Lerdrup
Nature communications | 2024

The timing of DNA replication in mammals is crucial for minimizing errors and influenced by genome usage and chromatin states. Replication timing in the newly formed mammalian embryo remains poorly understood. Here, we have investigated replication timing in mouse zygotes and 2-cell embryos, revealing that zygotes lack a conventional replication timing program, which then emerges in 2-cell embryos. This program differs from embryonic stem cells and generally correlates with transcription and genome compartmentalization of both parental genomes. However, consistent and systematic differences existed between the replication timing of the two parental genomes, including considerably later replication of maternal pericentromeric regions compared to paternal counterparts. Moreover, maternal chromatin modified by Polycomb Repressive Complexes in the oocyte, undergoes early replication, despite belonging to the typically late-replicating B-compartment of the genome. 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.

Pubmed ID: 39060312

Research resources used in this publication

Antibodies used in this publication

None found

Associated grants

  • Agency: Danmarks Grundforskningsfond (Danish National Research Foundation),
    Id: DNRF115
  • Agency: Novo Nordisk Fonden (Novo Nordisk Foundation),
    Id: NNF22OC0080710

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This is a list of tools and resources that we have found mentioned in this publication.


ChIP-seq (tool)

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