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

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. Off-centered 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. [Display omitted] •Formin 2-nucleated F-actin impacts both oocyte nuclear position and architecture•Cytoplasmic F-actin promotes nuclear envelope fluctuations•Nuclear envelope fluctuations impact chromatin motion inside the nucleus•Cytoskeleton-induced nuclear envelope fluctuations modulate the oocyte transcriptome Almonacid et al. show that the positioning of the nucleus in the center of the oocyte is essential for proper gene expression. Actin, which positions the nucleus centrally, also ensures proper nuclear shape, and promotes nuclear envelope and chromatin movements that fine-tune gene expression.