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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, 2149-2162 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Rif1 ; Early Mouse Embryos ; Lamina-associated Domains ; Replication Fork Speed ; Replication Timing ; Single-cell Repli-seq; Dna-replication; Rna-seq; Chromatin; Domains; Cells; Dynamics; Architecture; Initiation; Maintains; H3k4me3
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 1534-5807
e-ISSN 1878-1551
Zeitschrift Developmental Cell
Quellenangaben Band: 60, Heft: 16, Seiten: 2149-2162 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epigenetics and Stem Cells (IES)
CF Laboratory Animal Services (CF-LAS)
POF Topic(s) 30204 - Cell Programming and Repair
30202 - Environmental Health
Forschungsfeld(er) Stem Cell and Neuroscience
PSP-Element(e) G-506200-001
A-620000-008
Förderungen NIH
Horizon 2020 Marie Sklodowska-Curie grant agreement "ChromDesign"
NIH 4DN program
German Research Foundation (DFG)
Association
DOI 10.1016/j.devcel.2025.03.016
WOS ID 001554096200001
Scopus ID 105003267213
PubMed ID 40262611
Erfassungsdatum 2025-05-05
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