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

Autor: Halliwell JA; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. jhalliwell@sund.ku.dk., Martin-Gonzalez J; Core Facility for Transgenic Mice, Department of Experimental Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hashim A; Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway., Dahl JA; Department of Microbiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.; Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway., Hoffmann ER; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. eva@sund.ku.dk., Lerdrup M; DNRF Center for Chromosome Stability, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mlerdrup@sund.ku.dk.; Centre for Embryology and Healthy Development, University of Oslo, Oslo, Norway. mlerdrup@sund.ku.dk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 27; Vol. 15 (1), pp. 6323. Date of Electronic Publication: 2024 Jul 27.
DOI: 10.1038/s41467-024-50727-w
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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