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 centring 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-centring, shaped the nucleus while promoting nuclear envelope fluctuations and chromatin motion. Off-centred 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. Overall design: 2 samples of Fmn2 +/- oocytes, 50 oocytes each and 2 samples of Fmn 2-/- oocytes, 50 oocytes each. For each biological sample, 3 technical replicates were done.