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Active Fluctuations of the Nuclear Envelope Shape the Transcriptional Dynamics in Oocytes

Maria Almonacid, Adel Al Jord, Stephany El-Hayek, Alice Othmani, Fanny Coulpier, Sophie Lemoine, [...] Raphaël Voituriez, Auguste Genovesio, Marie-Hélène Verlhac

Summary

Nucleus position in cells can act as a developmental cue. Mammalian oocytes position their nucleus centrally using an F-actin-mediated pressure gradient.
The biological significance of nucleus centering in mammalian oocytes being unknown, we sought to assess the F-actin pressure gradient effect on the nucleus.
We addressed this using a dedicated computational 3D imaging approach, biophysical analyses, and a nucleus repositioning assay in mouse oocytes mutant for cytoplasmic F-actin.
We found that the cytoplasmic activity, in charge of nucleus centering, shaped the nucleus while promoting nuclear envelope fluctuations and chromatin motion. Offcentered nuclei in F-actin mutant oocytes were misshaped with immobile chromatin and modulated gene expression. Restoration of F-actin in mutant oocytes rescued nucleus architecture fully and gene expression partially. Thus, the F-actin-mediated pressure gradient also modulates nucleus dynamics in oocytes. Moreover, this study supports a mechano-transduction model whereby cytoplasmic microfilaments could modulate oocyte transcriptome, essential for subsequent embryo development.

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Developmental Cell 51, 1–13, October 21, 2019. doi.org/10.1016/j.devcel.2019.09.010