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.