Transient nuclear softening for zygotic gene activation in mice.

Two-cell stage nuclei in mice become profoundly soft and plastic, enabling major zygotic gene activation, and this deformability depends on LC3-driven clearance of lamin B1.

• Why it matters: Chromatin changes during early embryogenesis are well studied, but how nuclear mechanics during epigenetic reprogramming support zygotic transcription remains unclear.
• What they did: Using direct organelle capture plus biophysical manipulation, the study linked nuclear deformability to rapid lamin B1 clearance by LC3, then tested lamin B1 retention/overloading and an engineered molecular tether that stiffens nuclei.
• The result: Lamin B1 retention or tether-induced stiffening caused incomplete activation of zygotic genes and impaired development, whereas embryos that maintained deformability avoided transcriptional interference and showed active RNA polymerase II accumulation with coordinated locus positioning.

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