Epigenomic differentiation in mouse preimplantation nuclei of biparental, parthenote and cloned embryos.

Chromosomes, sub-chromosomal regions and genes are repositioned during cell differentiation to acquire a celltype- specific spatial organization. The constraints that are responsible for this cell-type-specific spatial genome positioning are unknown. In this study we addressed the question of whether epigenetic genome modifications may represent constraints to the acquisition of a specific nuclear organization. The organization of kinetochores, pericentric heterochromatin and the nucleolus was analysed in pre-implantation mouse embryos obtained by in-vitro fertilization (IVF), parthenogenetic activation (P) and nuclear transfer (NT) of differentiated somatic nuclei, which possess different epigenomes. Each stage of pre-implantation embryonic development is characterized by a stage-specific spatial organization of nucleoli, kinetochores and pericentric heterochromatin. Despite differences in the frequencies and the time-course of nuclear architecture reprogramming events, by the eight-cell stage P and NT embryos achieved the same distinct nuclear organization in the majority of embryos as observed for IVF embryos. At this stage the gametic or somatic nuclear architecture of IVF or P and NT embryos, respectively, is replaced by a common embryonic nuclear architecture. This finding suggests that the epigenome of the three types of embryos partially acts as a constraint of the nuclear organization of the three nuclear subcompartments analysed.