The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways

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  • dc.contributor.author Pal, Mrinmoy
  • dc.contributor.author Schauer, Tamas
  • dc.contributor.author Burton, Adam
  • dc.contributor.author Nakatani, Tsunetoshi
  • dc.contributor.author Pecori, Federico
  • dc.contributor.author Hernández-Giménez, Alicia
  • dc.contributor.author Nadelson, Iliya
  • dc.contributor.author Marti-Renom, Marc A.
  • dc.contributor.author Torres-Padilla, Maria-Elena
  • dc.date.accessioned 2025-09-02T06:30:36Z
  • dc.date.available 2025-09-02T06:30:36Z
  • dc.date.issued 2025
  • dc.description.abstract The folding of the genome in the 3D nuclear space is fundamental for regulating all DNA-related processes. The association of the genome with the nuclear lamina into lamina-associated domains (LADs) represents the earliest feature of nuclear organization during development. Here, we performed a gain-of-function screen in mouse embryos to obtain mechanistic insights. We find that perturbations impacting histone H3 modifications, heterochromatin, and histone content are crucial for the establishment of nuclear architecture in zygotes and/or 2-cell-stage embryos. Notably, some perturbations exerted differential effects on zygotes versus 2-cell-stage embryos. Moreover, embryos with disrupted LADs can rebuild nuclear architecture at the 2-cell stage, indicating that the initial establishment of LADs in zygotes might be dispensable for early development. Our findings provide valuable insights into the functional interplay between chromatin and structural components of the nucleus that guide genome-lamina interactions during the earliest developmental stages.
  • dc.description.sponsorship We thank I. de la Rosa Velazquez (Sequencing Facility, Helmholtz Munich), S. Krebs (LAFUGA, Gene Center), and V. Benes (EMBL SOLEXA) for sequencing; N. Battich for manuscript reading; S. Tripathi for helping with illustrations; and R. Grosse, M. Hetzer, P. Percipalle, J. Lammerding, T. Haraguchi, R. Schneider, M.H. Verlhac, and J. Whetstine for plasmids. Work in the M.-E.T.-P. laboratory is funded by the Helmholtz Association, the German Research Foundation (DFG) project-ID 213249687 (SFB1064), and the NIH 4DN program (grant 5U01DK127391-03). M.P., A.H.-G., M.A.M.-R., and M.-E.T.-P. acknowledge support from the EU Horizon 2020 research and innovation programme (Marie Sklodowska-Curie grant agreement 813327 “ChromDesign”).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Pal M, Schauer T, Burton A, Nakatani T, Pecori F, Hernández-Giménez A, et al. The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways. Cell. 2025 Jun 26;188(13):3583-602.e21. DOI: 10.1016/j.cell.2025.03.044
  • dc.identifier.doi http://dx.doi.org/10.1016/j.cell.2025.03.044
  • dc.identifier.issn 0092-8674
  • dc.identifier.uri http://hdl.handle.net/10230/71090
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof Cell. 2025 Jun 26;188(13):3583-602.e21
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/813327
  • dc.rights © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword 3D genome organization
  • dc.subject.keyword LAD
  • dc.subject.keyword MZT
  • dc.subject.keyword ZGA
  • dc.subject.keyword Epigenetics
  • dc.subject.keyword Mouse embryo
  • dc.subject.keyword Nuclear architecture
  • dc.title The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion