Genome–lamina interactions are established de novo in the early mouse embryo

Máté Borsos, Sara M. Perricone, Tamás Schauer, Julien Pontabry, Kim L. Luca, Sandra S. Vries, Elias R. Ruiz-Morales, Maria-Elena Torres-Padilla () and Jop Kind ()
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Máté Borsos: Helmholtz Zentrum München
Sara M. Perricone: Hubrecht Institute–KNAW and University Medical Center Utrecht
Tamás Schauer: Ludwig-Maximilians-University
Julien Pontabry: Helmholtz Zentrum München
Kim L. Luca: Hubrecht Institute–KNAW and University Medical Center Utrecht
Sandra S. Vries: Hubrecht Institute–KNAW and University Medical Center Utrecht
Elias R. Ruiz-Morales: Helmholtz Zentrum München
Maria-Elena Torres-Padilla: Helmholtz Zentrum München
Jop Kind: Hubrecht Institute–KNAW and University Medical Center Utrecht

Nature, 2019, vol. 569, issue 7758, 729-733

Abstract: Abstract In mammals, the emergence of totipotency after fertilization involves extensive rearrangements of the spatial positioning of the genome1,2. However, the contribution of spatial genome organization to the regulation of developmental programs is unclear3. Here we generate high-resolution maps of genomic interactions with the nuclear lamina (a filamentous meshwork that lines the inner nuclear membrane) in mouse pre-implantation embryos. We reveal that nuclear organization is not inherited from the maternal germline but is instead established de novo shortly after fertilization. The two parental genomes establish lamina-associated domains (LADs)4 with different features that converge after the 8-cell stage. We find that the mechanism of LAD establishment is unrelated to DNA replication. Instead, we show that paternal LAD formation in zygotes is prevented by ectopic expression of Kdm5b, which suggests that LAD establishment may be dependent on remodelling of H3K4 methylation. Our data suggest a step-wise assembly model whereby early LAD formation precedes consolidation of topologically associating domains.

Date: 2019
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DOI: 10.1038/s41586-019-1233-0

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