Abstract
In the early mammalian embryo, chromosomes are compartmentalised in a parent - of - origin specific manner, a feature thought to be important for their differential reprogramming Probst and Almouzni 1, 2-4. In mammals, pronuclei do not fuse after fertilisation but parental genomes are first replicated separately and then brought together after pronuclear envelope breakdown on the metaphase plate of the first mitosis 5,6. Strikingly, maternal and paternal chromatin occupies distinct hemispheres in the nuclei of the two-cell embryo, and this separation only gradually decreases during subsequent stages of development 4,7. Both the mechanism underlying parental genome separation and its functional importance for differential reprogramming are currently unclear. Here we reveal that the formation of two separate bipolar spindles around each parental pronucleus keeps maternal and paternal genomes apart during the first cleavage of the zygote. This mechanistic understanding allows us to test the requirement of genome separation for maintaining epigenetic asymmetry and its differential reprogramming by experimentally mixing the parental chromosomes. We show that establishment, maintenance and reprogramming of epigenetic asymmetry between the parental genomes is a chromosome intrinsic property and occurs independently of their compartmentalisation.
