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The establishment of nuclear organization in mouse embryos is orchestrated by multiple epigenetic pathways.
Cell 188, DOI: 10.1016/j.cell.2025.03.044 (2025)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
3d Genome Organization ; Lad ; Mzt ; Zga ; Epigenetics ; Mouse Embryo ; Nuclear Architecture
ISSN (print) / ISBN
0092-8674
e-ISSN
1097-4172
Journal
Cell
Quellenangaben
Volume: 188
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epigenetics and Stem Cells (IES)