Active fluctuations modulate gene expression in mouse oocytes

Abstract

In mammals, the nucleus is central in oocytes, not defining the future embryo axis. Nucleus centring depends on an F-actin mediated pressure gradient. In Fmn2-/- oocytes, lacking the F-actin nucleator Formin 2, the nucleus is off-centre and can be centred by re-expressing Formin 2. Here, we addressed the biological significance of nucleus positioning in mammalian oocytes. Using a dedicated computational 3D imaging approach, we observed nuclear architecture alterations in mouse Fmn2-/- oocytes. RNA sequencing of control versus Fmn2-/- oocytes detected 2285 mis-regulated genes. Rescue experiments showed that the process of nuclear positioning impacts nuclear architecture and gene expression. Using signal processing methods coupled to biophysical modelling allowing the extraction of in vivo mechanical properties of the nuclear envelope, we showed that F-actin-mediated activity promotes nuclear envelope shape fluctuations and chromatin motion. We thus propose a mechano-transduction model whereby nucleus positioning via microfilaments modulates oocyte transcriptome, essential for further embryo development.