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Nakatani, T. ; Schauer, T. ; Pal, M. ; Ettinger, A. ; Altamirano-Pacheco, L. ; Zorn, J. ; Gilbert, D.M.* ; Torres-Padilla, M.E.

RIF1 controls replication timing in early mouse embryos independently of lamina-associated nuclear organization.

Dev. Cell 60, DOI: 10.1016/j.devcel.2025.03.016 (2025)

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Cells must duplicate their genome before they divide to ensure equal transmission of genetic information. The genome is replicated with a defined temporal order, replication timing (RT), which is cell-type specific and linked to 3D-genome organization. During mammalian development, RT is initially not well defined and becomes progressively consolidated from the 4-cell stage. However, the molecular regulators are unknown. Here, by combining loss-of-function analysis with genome-wide investigation of RT in mouse embryos, we identify Rap1 interacting factor 1 (RIF1) as a regulator of the progressive consolidation of RT. Embryos without RIF1 show DNA replication features of an early, more totipotent state. RIF1 regulates the progressive stratification of RT values and its depletion leads to global RT changes and a more heterogeneous RT program. Developmental RT changes are disentangled from changes in transcription and nuclear organization, specifically nuclear lamina association. Our work provides molecular understanding of replication and genome organization at the beginning of mammalian development.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Rif1 ; Early Mouse Embryos ; Lamina-associated Domains ; Replication Fork Speed ; Replication Timing ; Single-cell Repli-seq

ISSN (print) / ISBN 1534-5807

e-ISSN 1878-1551

Journal Developmental Cell

Quellenangaben Volume: 60

Publisher Elsevier

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epigenetics and Stem Cells (IES)
CF Laboratory Animal Services (CF-LAS)